Nausea and vomiting of pregnancy and hyperemesis gravidarum

Abstract: Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.


Interventions for unexplained infertility: a systematic review and network meta-analysis

Marinus J C Eijkemans

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

Abstract:
BACKGROUND: Clinical management for unexplained infertility includes expectant management as well as active treatments, including ovarian stimulation (OS), intrauterine insemination (IUI), OS-IUI, and in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI).Existing systematic reviews have conducted head-to-head comparisons of these interventions using pairwise meta-analyses. As this approach allows only the comparison of two interventions at a time and is contingent on the availability of appropriate primary evaluative studies, it is difficult to identify the best intervention in terms of effectiveness and safety. Network meta-analysis compares multiple treatments simultaneously by using both direct and indirect evidence and provides a hierarchy of these treatments, which can potentially better inform clinical decision-making.

OBJECTIVES: To evaluate the effectiveness and safety of different approaches to clinical management (expectant management, OS, IUI, OS-IUI, and IVF/ICSI) in couples with unexplained infertility.

SEARCH METHODS: We performed a systematic review and network meta-analysis of relevant randomised controlled trials (RCTs). We searched electronic databases including the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane Central Register of Studies Online, MEDLINE, Embase, PsycINFO and CINAHL, up to 6 September 2018, as well as reference lists, to identify eligible studies. We also searched trial registers for ongoing trials.

SELECTION CRITERIA: We included RCTs comparing at least two of the following clinical management options in couples with unexplained infertility: expectant management, OS, IUI, OS-IUI, and IVF (or combined with ICSI).

DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardised forms. The primary effectiveness outcome was a composite of cumulative live birth or ongoing pregnancy, and the primary safety outcome was multiple pregnancy. We performed a network meta-analysis within a random-effects multi-variate meta-analysis model. We presented treatment effects by using odds ratios (ORs) and 95% confidence intervals (CIs). For the network meta-analysis, we used Confidence in Network Meta-analysis (CINeMA) to evaluate the overall certainty of evidence.

MAIN RESULTS: We included 27 RCTs (4349 couples) in this systematic review and 24 RCTs (3983 couples) in a subsequent network meta-analysis. Overall, the certainty of evidence was low to moderate: the main limitations were imprecision and/or heterogeneity.Ten RCTs including 2725 couples reported on live birth. Evidence of differences between OS, IUI, OS-IUI, or IVF/ICSI versus expectant management was insufficient (OR 1.01, 95% CI 0.51 to 1.98; low-certainty evidence; OR 1.21, 95% CI 0.61 to 2.43; low-certainty evidence; OR 1.61, 95% CI 0.88 to 2.94; low-certainty evidence; OR 1.88, 95 CI 0.81 to 4.38; low-certainty evidence). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) we found OS-IUI and IVF/ICSI increased live birth rate compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate-certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence).Eleven RCTs including 2564 couples reported on multiple pregnancy. Compared to expectant management/IUI, OS (OR 3.07, 95% CI 1.00 to 9.41; low-certainty evidence) and OS-IUI (OR 3.34 95% CI 1.09 to 10.29; moderate-certainty evidence) increased the odds of multiple pregnancy, and there was insufficient evidence of a difference between IVF/ICSI and expectant management/IUI (OR 2.66, 95% CI 0.68 to 10.43; low-certainty evidence). These findings suggest that if the chance of multiple pregnancy following expectant management or IUI is assumed to be 0.6%, the chance following OS, OS-IUI, and IVF/ICSI would be 0.6% to 5.0%, 0.6% to 5.4%, and 0.4% to 5.5%, respectively.Trial results show insufficient evidence of a difference between IVF/ICSI and OS-IUI for moderate/severe ovarian hyperstimulation syndrome (OHSS) (OR 2.50, 95% CI 0.92 to 6.76; 5 studies; 985 women; moderate-certainty evidence). This suggests that if the chance of moderate/severe OHSS following OS-IUI is assumed to be 1.1%, the chance following IVF/ICSI would be between 1.0% and 7.2%.

AUTHORS' CONCLUSIONS: There is insufficient evidence of differences in live birth between expectant management and the other four interventions (OS, IUI, OS-IUI, and IVF/ICSI). Compared to expectant management/IUI, OS may increase the odds of multiple pregnancy, and OS-IUI probably increases the odds of multiple pregnancy. Evidence on differences between IVF/ICSI and expectant management for multiple pregnancy is insufficient, as is evidence of a difference for moderate or severe OHSS between IVF/ICSI and OS-IUI.

The Cochrane database of systematic reviews


Increased Likelihood of Pregnancy Using an App-Connected Ovulation Test System: A  Randomized Controlled Trial

Sarah Johnson

Centers for Disease Control and Prevention

Abstract:
Background: Women trying to conceive are increasingly using fertility-tracking software applications to time intercourse. This study evaluated the difference in conception rates between women trying to conceive using an application-connected ovulation test system, which measures urinary luteinizing hormone and an estrogen metabolite, versus those trying without using ovulation testing.

Materials and Methods: This home-based study involved 844 volunteers aged 18-40 years seeking to conceive. Volunteers randomized to the test arm were required to use the test system for the duration of the study while those randomized to the control arm were instructed not to use ovulation testing. Pregnancy rate differences across one and two cycles between the two groups were examined.

Results: Volunteers in the test (n = 382) and control arms (n = 403) had similar baseline demographics. The proportion of women pregnant after one cycle was significantly greater in the test arm (25.4%) compared with the control arm (14.7%; p < 0.001). After two cycles, there continued to be a greater proportion of women pregnant in the test arm compared with the control arm (36.2% vs. 28.6%; p = 0.026). In the test arm, volunteers had intercourse less frequently per cycle compared with those not using ovulation testing (9 [range: 1-60] vs. 10 [range: 1-50]; p = 0.027), but were more likely to target intercourse to a particular part of their cycle compared with those not using ovulation testing (88.5% vs. 57.8%; p < 0.001).

Conclusion: Using the test system to time intercourse within the fertile window increases the likelihood of conceiving within two menstrual cycles.


Physical Activity and the Occurrence of Postnatal Depression-A Systematic Review

Abstract: Background and Objectives: During pregnancy and the postnatal period many changes occur in a woman's body, both in mental and physical spheres. The birth of a child and a new role-of a mother-can sometimes be associated with numerous negative emotions, uncertainty, fear, anxiety, disgust, depression, or sadness. In the puerperium period, the development of baby blues or postpartum depression may occur. Postpartum depression develops within one month of childbirth and may last up to one year. Depressive disorders that may develop in a young mother affect both her and the newborn's health. That is why it is so important to try to search for factors that could significantly reduce the likelihood of developing depression in this period. The study aims at assessing the relationship between physical activity during pregnancy and puerperium or in the postpartum and the development of postnatal depression. Materials and Methods: A review of the literature was carried out in the Medline-PubMed database. The search terms were "pregnancy" AND "physical activity AND postpartum depression". The study included only English-language publications published in the period 2000-2018. Results: A total of 216 references were found. After establishing the inclusion and exclusion criteria based on the analysis of titles and abstracts, 173 articles were excluded from the review. A total of 43 publications were read in full. Finally, 16 articles were included in the review. It was shown that regular physical activity during pregnancy, pregnancy, and puerperium, or in the postnatal period itself as compared to inactivity, reduces the risk of developing depression in pregnant women and after the birth of a child. Conclusions: Physical activity can be an essential factor in the prevention of depressive disorders of women in the postnatal period.


Endometriosis and Risk of Adverse Pregnancy Outcomes

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Audrey J Gaskins

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia. Electronic address: Audrey.jane.gaskins@emory.edu.

Abstract:
OBJECTIVE:
To investigate the relationship between endometriosis and adverse pregnancy outcomes.

METHODS:
Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman.

RESULTS:
Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45).

CONCLUSIONS:
We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.


Phthalates in infant cotton clothing: Occurrence and implications for human exposure

Zhiqiang Zhang

Tianjin Medical University General Hospital

Abstract: Clothing easily adsorbed the chemicals in the environment, and became a source of human exposure to chemicals. However, large contacted surface area and long exposure duration have elevated human exposure to chemicals from clothing, such as phthalates. Among them, cotton clothing, which infants prefer to wear, has been proven to adsorb phthalates more easily than other fabrics. While infants are developing, they are easily affected by phthalates. In this study, in order to study accumulation of phthalates in infant cotton clothing during the whole process from production to the first wearing, 24 infant cotton clothing samples were collected from shopping malls in Harbin, China. High detection rates and concentrations suggest that phthalates in the environment are widely adsorbed to infant cotton clothing, and traditional laundering for infant clothing cannot remove phthalates completely. The median concentration of the total phthalates was 4.15 μg/g. Di-(2-ethylhexyl) phthalate (DEHP) has become the dominant phthalate. For the estimated daily intakes (EDIs) for infants, dibutyl phthalate (DBP) had the highest contribution, followed by di-iso-butyl phthalate (DiBP) and DEHP. Dermal absorption has become the main route of infant exposure to phthalates, and ingestion contributed very little. The result of comparing with the EDIs via dermal absorption from house air and dust suggests that clothing plays an important role of dermal absorption exposure to phthalates. For risk assessment, the carcinogenic risk of BBP and DEHP indicates that the level of DEHP in infant cotton clothing might pose potential adverse effects to infant health.


Association between peri-conceptional bisphenol A exposure in women and men and  time to pregnancy-The HOPE study

Abstract:
Background: Bisphenol A (BPA) is a non-persistent endocrine-disrupting chemical with nearly ubiquitous, involuntary exposure. Previous studies have shown that BPA causes reproductive dysfunction in animal models, but there are limited data regarding the effects of BPA exposure on time to pregnancy (TTP) in humans.

Objective: To evaluate whether peri-conceptional BPA exposure of women and men is associated with couples' TTP.

Methods: A total of 164 heterosexual couples (164 women; 163 men) who have available BPA information as well as time to pregnancy from the Home Observation of Peri-conceptional Exposures (HOPE) Study were included and were followed up to 12 months. Women collected first-morning urine samples starting at the beginning of the fertile window and continued until the onset of menses or 18 days after the estimated day of ovulation (EDO+18 days). The time to pregnancy (TTP) after the enrolment was self-reported and used for the analysis. Discrete-time Cox proportional hazards models were performed to generate fecundability odds ratio (FOR) between BPA and TTP after adjusting for education and age, accounting for right censoring and prior number of cycles trying to conceive.

Results: Among 164 couples, 125 couples became pregnant during the study. There was no association between TTP and peri-conceptional BPA exposure for both men (FOR 1.02, 95% CI 0.72, 1.47) and women (FOR 1.07, 95% CI 0.75, 1.53) after adjusting for education and age.

Conclusions: No association was found between peri-conceptional BPA exposure and fecundability in this preconception cohort of relatively young, healthy pregnancy planners.


Pathological pulses in PCOS

Pathological pulses in PCOS

Rebecca E Campbell

Centre for Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, 9054, New Zealand. Electronic address: rebecca.campbell@otago.ac.nz.

Abstract: Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder associated with hyperandrogenism and anovulation. Although a spectrum disorder, many women with PCOS exhibit elevated luteinizing hormone (LH) pulse frequency and an elevated LH to follicle stimulating hormone ratio. This aberrant pattern of gonadotrophin signalling drives many of the downstream ovarian features of PCOS, including increased androgen synthesis, and indicates neuroendocrine impairments upstream. Decreased responsiveness to gonadal steroid hormone negative feedback in PCOS patients points toward dysfunction within the gonadotropin-releasing hormone (GnRH) neuronal network in the brain. Excessive androgen exposure during development or over pubertal onset can recapitulate the neuroendocrine pathology of PCOS in pre-clinical models, and these models have been fundamental in beginning to pick apart the specific central mechanisms involved. This mini-review will briefly describe the pathology of PCOS associated with high frequency GnRH/LH pulses and then highlight what is currently known, and yet to be discovered, about the central mechanisms involved.


Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring: A Systematic Review and Meta-analysis

Laura Sevilla-Cermeño

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

David Mataix-Cols

Abstract:
IMPORTANCE: Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete.

OBJECTIVE: To evaluate the association between cesarean delivery and risk of neurodevelopmental and psychiatric disorders in the offspring.

DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception to December 19, 2018. Search terms included all main mental disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).

STUDY SELECTION: Two researchers independently selected observational studies that examined the association between cesarean delivery and neurodevelopmental and psychiatric disorders in the offspring.

DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines and assessed study quality using the Newcastle-Ottawa Scale. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% CIs for each outcome. Sensitivity and influence analyses tested the robustness of the results.

MAIN OUTCOMES AND MEASURES: The ORs for the offspring with any neurodevelopmental or psychiatric disorder who were born via cesarean delivery compared with those were born via vaginal delivery.

RESULTS: A total of 6953 articles were identified, of which 61 studies comprising 67 independent samples were included, totaling 20 607 935 deliveries. Compared with offspring born by vaginal delivery, offspring born via cesarean delivery had increased odds of autism spectrum disorders (OR, 1.33; 95% CI, 1.25-1.41; I2 = 69.5%) and attention-deficit/hyperactivity disorder (OR, 1.17; 95% CI, 1.07-1.26; I2 = 79.2%). Estimates were less precise for intellectual disabilities (OR, 1.83; 95% CI, 0.90-3.70; I2 = 88.2%), obsessive-compulsive disorder (OR, 1.49; 95% CI, 0.87-2.56; I2 = 67.3%), tic disorders (OR, 1.31; 95% CI, 0.98-1.76; I2 = 75.6%), and eating disorders (OR, 1.18; 95% CI, 0.96-1.47; I2 = 92.7%). No significant associations were found with depression/affective psychoses or nonaffective psychoses. Estimates were comparable for emergency and elective cesarean delivery. Study quality was high for 82% of the cohort studies and 50% of the case-control studies.

CONCLUSIONS AND RELEVANCE: The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted.


Oral contraceptive use in adolescence predicts lasting vulnerability to  depression in adulthood

Frances S Chen

Department of Psychology University of British Columbia Vancouver BC Canada

Abstract:
Background: Previous evidence suggests that use of oral contraceptives (OCs), especially during adolescence, may increase women's vulnerability to depression in the short term. Here, we investigate whether women who had first used OC in adolescence show an increased prevalence of depression in the long term.

Methods: We examined 1,236 women in the United States National Health and Nutrition Examination Survey for whom information on depression and age at first OC use was publicly available. We compared women who reported first use of OCs in adolescence to women who had never used OCs and women who had first used OCs in adulthood on 1-year prevalence of major depressive disorder (MDD) assessed by trained interviewers.

Results: Compared with women who had used OCs during adolescence, women who had never used OCs were less likely to meet the criteria for MDD within the past year in adulthood [odds ratio (OR) = 0.31, 95% CI = 0.16-0.60], and so were women who only started using OCs in adulthood (OR = 0.54, 95% CI = 0.30-0.95). Third factors that have previously been proposed to explain the relationship between OC use and depression risk such as age at sexual debut, and, importantly, current OC use, did not account for the results in propensity score analyses.

Conclusions: We show a long-term association between adolescent OC use and depression risk in adulthood regardless of current OC use. Our findings suggest that adolescence may be a sensitive period during which OC use could increase women's risk for depression, years after first exposure.

Journal of Child Psychology and Psychiatry, and Allied Disciplines


Big data meets the menstrual cycle

Big data meets the menstrual cycle


Perinatal Palliative Care: ACOG COMMITTEE OPINION, Number 786

Abstract: Perinatal palliative care refers to a coordinated care strategy that comprises options for obstetric and newborn care that include a focus on maximizing quality of life and comfort for newborns with a variety of conditions considered to be life-limiting in early infancy. With a dual focus on ameliorating suffering and honoring patient values, perinatal palliative care can be provided concurrently with life-prolonging treatment. The focus of this document, however, involves the provision of exclusively palliative care without intent to prolong life in the context of a life-limiting condition, otherwise known as perinatal palliative comfort care. Once a life-limiting diagnosis is suspected antenatally, the tenets of informed consent require that the pregnant patient be given information of sufficient depth and breadth to make an informed, voluntary choice for her care. Health care providers are encouraged to model effective, compassionate communication that respects patient cultural beliefs and values and to promote shared decision making with patients. Perinatal palliative comfort care is one of several options along a spectrum of care, which includes pregnancy termination (abortion) and full neonatal resuscitation and treatment, that should be presented to pregnant patients faced with pregnancies complicated by life-limiting fetal conditions. If a patient opts to pursue perinatal palliative comfort care, a multidisciplinary team should be identified with the infrastructure and support to administer this care. The perinatal palliative care team should prepare families for the possibility that there may be differences of opinion between family members before and after the delivery of the infant, and that there may be differences between parents and the neonatal care providers about appropriate postnatal therapies, especially if the postnatal diagnosis and prognosis differ substantially from antenatal predictions. Procedures for resolving such differences should be discussed with families ahead of time.


Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Stephanie Kaiser

Department of Medicine, Dalhousie University, Halifax, Canada.

Christopher S Kovacs

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Jacqueline R Center

Faculty of MedicineUniversity of New South WalesSydneyAustralia

Joop van den Bergh

Department of Internal MedicineVieCuri Medical Centre of Noord-LimburgVenloThe Netherlands

Tineke van Geel

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

Abstract: Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients.


Worldwide decline of IVF birth rates and its probable causes

Abstract: With steadily improving pregnancy and live birth rates, IVF over approximately  the first two and a half decades evolved into a highly successful treatment for  female and male infertility, reaching peak live birth rates by 2001-2002.  Plateauing rates, thereafter, actually started declining in most regions of the  world. We here report worldwide IVF live birth rates between 2004 and 2016,  defined as live births per fresh IVF/ICSI cycle started, and how the  introduction of certain practice add-ons in timing was associated with changes  in these live birth rates. We also attempted to define how rapid worldwide  'industrialization' (transition from a private practice model to an  investor-driven industry) and 'commoditization' in IVF practice (primary  competitive emphasis on revenue rather than IVF outcomes) affected IVF outcomes.  The data presented here are based on published regional registry data from  governments and/or specialty societies, covering the USA, Canada, the UK,  Australia/New Zealand (combined), Latin America (as a block) and Japan. Changes  in live birth rates were associated with introduction of new IVF practices,  including mild stimulation, elective single embryo transfer (eSET), PGS (now  renamed preimplantation genetic testing for aneuploidy), all-freeze cycles and  embryo banking. Profound negative associations were observed with mild  stimulation, extended embryo culture to blastocyst and eSET in Japan,  Australia/New Zealand and Canada but to milder degrees also elsewhere. Effects  of 'industrialization' suggested rising utilization of add-ons  ('commoditization'), increased IVF costs, reduced live birth rates and poorer  patient satisfaction. Over the past decade and a half, IVF, therefore, has  increasingly disappointed outcome expectations. Remarkably, neither the  profession nor the public have paid attention to this development which,  therefore, also has gone unexplained. It now urgently calls for evidence-based  explanations.


Maternity homes and social support: A cross-sectional survey stratifying  outcomes

Cara Buskmiller

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

Abstract: Poor social support is associated with adverse obstetric outcomes. Maternity group homes (MGHs), residential programs for pregnant women, have been found to improve social support in small studies. The present study aimed to verify these previous studies, discover whether there is a group of women whom MGHs most benefit, identify what services offer that benefit, and identify how to predict who will most benefit from MGH admission. Forty-three US MGHs from 14 states were surveyed from August 2015 to February 2017. The primary outcome was self-reported social support before and during MGH admission. The secondary outcome was the perception that MGH admission would help current and future relationships. Among 95 respondents, 54% perceived better in-MGH support compared to pre-MGH support. Women with poor pre-MGH support reported improvement; the converse was true of high pre-MGH support (P < 0.001). A total of 77% to 82% of participants anticipated that MGH admission would help current and future relationships, including 91% to 92% of women with stable or increased in-MGH support (P = 0.07 current, P < 0.01 future). Participants with increased in-MGH support reported more services as helpful (P < 0.05). In summary, MGHs are associated with improved support and relationships for most residents. The support score may identify which women may benefit most from MGH admission.

Proceedings (Baylor University. Medical Center)


Endometriosis

Endometriosis

Shimeng Liu

Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Abstract: Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.


Response to Letter to the Editor: "Progesterone Is Important for Transgender Women's Therapy-Applying Evidence for the Benefits of Progesterone in Ciswomen"

The Journal of clinical endocrinology and metabolism


Duration of Hormonal Contraception and Risk of Cervical Cancer

Heni Puji Wahyuningsih

Ministry of Health of the Russian Federation

Abstract: The use of long hormonal contraceptives can disrupt the balance of estrogen in the body, resulting in abnormal cell changes. This study aimed to determine a correlation between the duration of hormonal contraception and risk of cervical cancer. This study used a case-control design. The population were patients who had examined at a cancer installation and obstetrics-gynecology polyclinic Dr. Sardjito Hospital in 2018. Case samples were 95 women have cervical cancer diagnosis and control were 95 women with a negative pap smear. Sampling with random sampling. Dependent variable cervical cancer and independent variable the duration of hormonal contraception are obtained from medical records. Cervical cancer is assessed by doctor’s diagnosis. Data analysis used logistic regression. Results showed that 44.7% of samples used long-term hormonal contraception (over 5 years). Length of use of hormonal contraception had a significant correlation with the incidence of cervical cancer (p-value < 0.01). Hormonal contraceptive use more than 5 years have a risk 4.2 times (95% CI 1.01-5.69) of cervical cancer than using less than 5 years after being controlled with the first marriage age and parity


Previous contraceptive treatment relates to grey matter volumes in the  hippocampus and basal ganglia

Esmeralda Hidalgo-Lopez

Department of Psychology & Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria.

Abstract: Oral contraceptive (OC) effects on the brain have gained increasing interest, but are highly controversial. Previous studies suggest that OC users have larger hippocampi, parahippocampi, fusiform gyri and Cerebelli. Preliminary evidence from one of those studies even suggests an effect of previous contraceptive use on the hippocampi of women who are not current users of OCs. Furthermore, more recent studies postulate an involvement of previous OC treatment in later development of mood disorders. To address the question whether previous OC treatment affects women's brain structure later in life, high resolution structural images were obtained from 131 naturally cycling women. Among them, 52 women had never used OC before, 52 had previously used one OC for a continuous time period and 27 had previously used multiple contraceptives. The groups did not differ in gray matter volumes. Since endogenous sex hormones modulate gray matter volumes of the hippocampus and basal ganglia along the menstrual cycle, we hypothesize effects of OC use on these areas. Specifically, we hypothesize that a longer duration of previous OC treatment is related to larger hippocampi and larger basal ganglia. Indeed we found the duration of previous OC use to be positively correlated to hippocampal and basal ganglia volumes bilaterally. For the hippocampus, but not for the basal ganglia, this association disappeared after controlling for the time since discontinuation. These results suggest that for the hippocampus, but not for the basal ganglia, effects of previous contraceptive treatment are reversed after a time period comparable to treatment duration. These data question the immediate reversibility of OC effects on brain structure. Accordingly, some changes in the brain due to long-term contraceptive use, while subtle, may be long-lasting.


Medical diligence uncovers fallopian tube cancer after abnormal Pap test

Abstract: The fallopian tube has received attention as an origin of high-grade pelvic malignancies. This is a case of bilateral fallopian tube cancer discovered after an abnormal Pap test. A 62-year-old woman with a history of one term delivery had atypical glandular cells on a Pap test. She had an unsatisfactory colposcopy and a normal transvaginal ultrasound. A loop electrode excision procedure and hysteroscopy with dilation and curettage revealed atypical glandular cells concentrated in floating balls. CA-125 was 10 U/mL. A robotic hysterectomy revealed histopathological stage IIIA serous carcinoma arising from both fallopian tubes. She received six cycles of carboplatin and paclitaxel. After chemotherapy, she has no evidence of disease at 5 years. Fallopian tube carcinoma is a differential diagnosis of abnormal glandular cells on a Pap test. Diagnosis by systematic pursuit of abnormal tests can lead to successful treatment of a small disease burden.


Fertility and pregnancy outcomes following hysteroscopic metroplasty of different  sized uterine septa: A retrospective cohort study protocol

Abstract: Different sizes of uterine septum between infertile women and patients with abortions may have a clinical relevance in reproductive performance after surgery. This study aimed to assess if the fecundity of women after surgical correction of the uterine septum is associated with septum size.A retrospective, single-center, cohort study was conducted in Peking Union Medical College Hospital using patients aged between 21 and 37 years. Hysteroscopic metroplasty was performed on 121 patients with a uterine septum. The septum size was assessed by ultrasonography and hysteroscopy. The subjects were divided into 3 groups: Group A consisted of 35 women with complete uterine septum (mean ± standard deviation (SD) age 28.29 ± 3.53; group B consisted of 48 women with uterine septum >2.5 cm (mean ± SD age 28.85 ± 3.63); and group C consisted of 48 women with uterine septum ≤2.5 cm (mean ± SD age 28.79 ± 3.74). Age and body mass index (BMI) were not significantly different among the 3 groups.No serious hysteroscopic complications occurred. However, uterine septa were observed in 4 cases after surgery and 6 cases of intrauterine adhesions were observed after long-term follow-up. The abortion rate decreased, and term delivery rate increased significantly in the 3 groups after hysteroscopic metroplasty. The infertility rate was significantly lower in group C after surgery. However, no significant difference was observed in the infertility rate between groups A and B. The recurrent abortion rate was significantly lower in group A than in groups B and C before surgery. After surgery, the infertility rate was significantly higher in group A than in group B (28.57% and 10.53%, respectively; P = .048). After at least 12-months of follow-up, the pregnancy rate in group A was significantly lower than that in group C (71.43% and 89.47%, respectively; P = .048).Uterine septum resection improves obstetrical outcomes. After surgery, the infertility rate was significantly higher in patients with complete uterine septum than in those with a large partial uterine septum, and the pregnancy rate in patients with complete uterine septum was lower than that in the patients with a small partial uterine septum.


Assessment of menstrual health status and evolution through mobile apps for  fertility awareness

Marcel Salathé

École Polytechnique Fédérale de Lausanne

Abstract: For most women of reproductive age, assessing menstrual health and fertility typically involves regular visits to a gynecologist or another clinician. While these evaluations provide critical information on an individual's reproductive health status, they typically rely on memory-based self-reports, and the results are rarely, if ever, assessed at the population level. In recent years, mobile apps for menstrual tracking have become very popular, allowing us to evaluate the reliability and tracking frequency of millions of self-observations, thereby providing an unparalleled view, both in detail and scale, on menstrual health and its evolution for large populations. In particular, the primary aim of this study was to describe the tracking behavior of the app users and their overall observation patterns in an effort to understand if they were consistent with previous small-scale medical studies. The secondary aim was to investigate whether their precision allowed the detection and estimation of ovulation timing, which is critical for reproductive and menstrual health. Retrospective self-observation data were acquired from two mobile apps dedicated to the application of the sympto-thermal fertility awareness method, resulting in a dataset of more than 30 million days of observations from over 2.7 million cycles for two hundred thousand users. The analysis of the data showed that up to 40% of the cycles in which users were seeking pregnancy had recordings every single day. With a modeling approach using Hidden Markov Models to describe the collected data and estimate ovulation timing, it was found that follicular phases average duration and range were larger than previously reported, with only 24% of ovulations occurring at cycle days 14 to 15, while the luteal phase duration and range were in line with previous reports, although short luteal phases (10 days or less) were more frequently observed (in up to 20% of cycles). The digital epidemiology approach presented here can help to lead to a better understanding of menstrual health and its connection to women's health overall, which has historically been severely understudied.


The association between hormones and antipsychotic use: a focus on postpartum and  menopausal women

Alexandre González-Rodríguez

Centro de Investigación Biomédica en Red de Salud Mental

Abstract: During the postpartum and menopausal periods of women's lives, there is a well-established and significant drop of circulating estrogens. This may be the reason why both these periods are associated with an increased risk for onset or exacerbation of psychiatric disorders. Whether symptoms are mainly affective or mainly psychotic, these disorders are frequently treated with antipsychotic medications, which calls for an examination of the relationship between hormone replacement and antipsychotic agents at these time periods. The aim of this narrative review is to summarize what is known about the association of hormones and antipsychotics in the postnatal period and at menopause. In the review, we focus on estrogen and oxytocin hormones and include, for the most part, only papers published within the last 10 years. Both estradiol and oxytocin have at various times been implicated in the etiology of postpartum disorders, and estrogens, sometimes combined with progesterone, have been tested as potential treatments for these conditions. The role of estradiol as an adjunct to antipsychotics in the prevention of postpartum relapses is currently controversial. With respect to oxytocin, studies are lacking. Psychosis in menopausal and postmenopausal women has been successfully treated with estrogens and selective estrogen-receptor modulators, mainly raloxifene, in addition to antipsychotics. Some symptoms appear to respond better than others. No oxytocin study has specifically targeted postmenopausal women. Because of feedback mechanisms, there is a theoretical danger of therapy with exogenous hormones interfering with endogenous secretion and disturbing the balance among inter-related hormones. When used with antipsychotics, hormones may also affect the metabolism and, hence, the brain level of specific antipsychotics. This makes treatment with antipsychotics plus hormones complicated. Dose, timing and route of intervention may all prove critical to efficacy. While much remains unknown, this literature review indicates that, within standard dose ranges, the combination of hormones and antipsychotics for postnatal and menopausal women suffering severe mental distress can be beneficial, and is safe.

Therapeutic Advances in Psychopharmacology


Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility

Abstract: Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.


Screening of textile finishing agents available on the Chinese market: An important source of per- and polyfluoroalkyl substances to the environment

Wenjuan Li

Ministry of Agriculture and Rural Affairs

Abstract: Organofluorinated surfactants are widely employed in textile finishing agents (TFAs) to achieve oil, water, and stain repellency. This has been regarded as an important emission source of per-and polyfluoroalkyl substances (PFASs) to the environment. China is the biggest manufacturer of clothes, and thus TFA production is also a relevant industrial activity. Nevertheless, to date, no survey has been conducted on PFAS contents in commercially available TFAs. In the present study, TFA products were investigated by the Kendrick mass defect method. The quantification results demonstrated a significant presence of perfluorooctane sulfonate (0.37 mg/L) in TFAs manufactured by electrochemical fluorination technology. The products obtained by short-chain PFAS-based telomerization were dominated by perfluorooctanoic acid (mean concentration: 0.29 mg/L), whose values exceeded the limits stated in the European Chemical Agency guidelines (0.025 mg/L). Moreover, the total oxidizable precursor assay indicated high levels of indirectly quantified precursors with long alkyl chains (C7-C9). Together, these results suggest that there is currently a certain of environmental and health risks in China that originates from the utilization of TFAs, and a better manufacturing processes are required to reduce such risks.

Frontiers of Environmental Science & Engineering


Fertility awareness based methods for pregnancy prevention

Abstract: ### What you need to know Fertility awareness based methods of contraception are increasingly being used for pregnancy prevention.1 In the US, the proportion of contraceptive users who choose such methods has grown from 1% in 2008 to approximately 3% in 2014.12 Relative to other methods of pregnancy prevention, however, substantial misinformation exists around fertility awareness based methods of contraception, particularly about the effectiveness of specific methods and how to use them. Providers who offer family planning counselling can promote correct and consistent use of the chosen method by helping people find a method that best fits their individual lifestyle, preferences, and goals.3 This article aims to help clinicians counsel people about fertility awareness based methods for pregnancy prevention by explaining the different methods, the evidence base for their effectiveness, and practical considerations for use. Fertility awareness based methods are devised on the premise that sexual intercourse can only lead to pregnancy during approximately 6-9 days of the menstrual cycle, commonly referred to as the “fertile window” (or fecund window, box 1).5 …


Could exotic mosquito-borne diseases emerge in Canada with climate change?

L R Lindsay

National Microbiology Laboratory, Public Health Agency of Canada, Guelph, ON, St. Hyacinthe, QC and Winnipeg, MB.

Abstract: Of the 3,500 species of mosquitoes worldwide, only a small portion carry and transmit the mosquito-borne diseases (MBDs) that cause approximately half a million deaths annually worldwide. The most common exotic MBDs, such as malaria and dengue, are not currently established in Canada, in part because of our relatively harsh climate; however, this situation could evolve with climate change. Mosquitoes native to Canada may become infected with new pathogens and move into new regions within Canada. In addition, new mosquito species may move into Canada from other countries, and these exotic species may bring exotic MBDs as well. With high levels of international travel, including to locations with exotic MBDs, there will be more travel-acquired cases of MBDs. With climate change, there is the potential for exotic mosquito populations to become established in Canada. There is already a small area of Canada where exotic Aedes mosquitoes have become established although, to date, there is no evidence that these carry any exotic (or already endemic) MBDs. The increased risks of spreading MBDs, or introducing exotic MBDs, will need a careful clinical and public health response. Clinicians will need to maintain a high level of awareness of current trends, to promote mosquito bite prevention strategies, and to know the laboratory tests needed for early detection and when to report laboratory results to public health. Public health efforts will need to focus on ongoing active surveillance, public and professional awareness and mosquito control. Canadians need to be aware of the risks of acquiring exotic MBDs while travelling abroad as well as the risk that they could serve as a potential route of introduction for exotic MBDs into Canada when they return home.

Canada Communicable Disease Report = Releve Des Maladies Transmissibles Au Canada


A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in  Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma  Treatment

Konstantinos Pantos

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

Mara Simopoulou

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

Athanasios Pappas

Centre for Human Reproduction, Genesis Athens Clinic, Greece.

Nikolaos Nitsos

Microbiology-Biochemical Department, Genesis Athens Clinic, Greece

Agni Pantou

Abstract: Since the introduction of autologous platelet-rich plasma (PRP) in medical practice, various studies have documented that implementing PRP can enhance healing and the anti-aging process, employing angiogenesis regeneration due to the multiple growth factors and cytokines involved. Numerous reports have shown promising results with the use of PRP in ovarian treatment, regarding ovarian regeneration and reactivation of folliculogenesis. This case series reports on two women with premature ovarian failure (POF) aged 40 and 27 years, respectively, and one menopausal woman aged 46 years. All patients presented with lack of menstrual cycle for over a year. The women reported previous failed in vitro fertilization (IVF) attempts, and, after rejecting the option of oocyte donation, they opted for the approach of autologous ovarian PRP treatment. Following PRP treatment, the three patients were invited to conceive naturally. The primary outcome was the restoration of menstruation following autologous ovarian PRP treatment, as well as an improvement in hormonal profile, a decrease in follicle-stimulating hormone (FSH) levels, and a concurrent increase in anti-Müllerian hormone (AMH) levels. Further to that, our patients achieved pregnancy through natural conception within 2-6 months following PRP treatment, resulting in currently ongoing complication-free clinical pregnancies - a first report in the literature for menopausal and POF patients. Implementation of PRP should be further investigated through randomized controlled trials (RCTs), as it may hold the key to successful treatment for a certain cohort of patients exploring reproductive treatment options following menopause.


Pilot Evaluation of a New Urine Progesterone Test to Confirm Ovulation in Women Using a Fertility Monitor

Abstract:
Background: Progesterone rises \~24-36 h after ovulation. Past studies using ultrasound-confirmed ovulation have shown that three consecutive tests with a threshold of 5μg/mL of urine progesterone (pregnanediol-3-glucuronide, PDG), taken after the luteinizing hormone (LH) surge, confirmed ovulation with 100% specificity.

Purpose: The purpose of this study was to a evaluate a new urine PDG self-test to retrospectively confirm ovulation in women who were monitoring ovulation using a hormonal fertility monitor.

Methods: Thirteen women of reproductive age were recruited to test urine PDG while using their home hormonal fertility monitor. The monitor measured the rise in estrogen (estrone-3-glucuronide, E3G) and LH to estimate the fertile phase of the menstrual cycle. The women used an online menstrual cycle charting system to track E3G, LH and PDG levels for four menstrual cycles.

Results: The participants (Mean age 33.6) produced 34 menstrual cycles of data (Mean length 28.4 days), 17 of which used a PDG test with a threshold of 7μg/mL and 17 with a threshold of 5μg/mL. In the cycles that used the 7μg/mL test strips, 59% had a positive confirmation of ovulation, and with the 5μg/mL test strips, 82% of them had a positive confirmation of ovulation.

Conclusion: The 5μg/mL PDG test confirmed ovulation in 82% of cycles and could assist women in the evaluation of the luteal progesterone rise of their menstrual cycle.


Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis

Stephanie Huberlant

Centre Hospitalier Universitaire de Nîmes

Abstract:
BACKGROUND: A worldwide increase in the prevalence of obesity has been observed in the past three decades, particularly in women of reproductive age. Female obesity has been clearly associated with impaired spontaneous fertility, as well as adverse pregnancy outcomes. Increasing evidence in the literature shows that obesity also contributes to adverse clinical outcomes following in vitro fertilization (IVF) procedures. However, the heterogeneity of the available studies in terms of populations, group definition and outcomes prevents drawing firm conclusions. A previous meta-analysis published in 2011 identified a marginal but significant negative effect of increased female body mass index (BMI) on IVF results, but numerous studies have been published since then, including large cohort studies from national registries, highlighting the need for an updated review and meta-analysis.

OBJECTIVE AND RATIONALE: Our systematic review and meta-analysis of the available literature aims to evaluate the association of female obesity with the probability of live birth following IVF. Subgroup analyses according to ovulatory status, oocyte origin, fresh or frozen-embryo transfer and cycle rank were performed.

SEARCH METHODS: A systematic review was performed using the following key words: ('obesity', 'body mass index', 'live birth', 'IVF', 'ICSI'). Searches were conducted in MEDLINE, EMBASE, Cochrane Library, Eudract and clinicaltrial.gov from 01 January 2007 to 30 November 2017. Study selection was based on title and abstract. Full texts of potentially relevant articles were retrieved and assessed for inclusion by two reviewers. Subsequently, quality was assessed using the Newcastle-Ottawa Quality Assessment Scales for patient selection, comparability and assessment of outcomes. Two independent reviewers carried out study selection and data extraction according to Cochrane methods. Random-effect meta-analysis was performed using Review Manager software on all data (overall analysis), followed by subgroup analyses.

OUTCOMES: A total of 21 studies were included in the meta-analysis. A decreased probability of live birth following IVF was observed in obese (BMI ≥ 30 kg/m2) women when compared with normal weight (BMI 18.5-24.9 kg/m2) women: risk ratio (RR) (95% CI) 0.85 (0.82-0.87). Subgroups analyses demonstrated that prognosis was poorer when obesity was associated with polycystic ovary syndrome, while the oocyte origin (donor or non-donor) did not modify the overall interpretation.

WIDER IMPLICATIONS: Our meta-analysis clearly demonstrates that female obesity negatively and significantly impacts live birth rates following IVF. Whether weight loss can reverse this deleterious effect through lifestyle modifications or bariatric surgery should be further evaluated.


Relationship of maximum follicular size, age of woman, and reproductive implications in women attending fertility clinic in St. Margaret's Hospital, Lokoja, using Creighton Model FertilityCare™ System and NaProTECHNOLOGY

Abstract:
Background: Some authorities have found that, when the mean follicular diameter is >25 mm, the follicle is considered large, and these authorities are convinced that large follicles are biomarkers to ovarian pathology. Several studies have been carried out to determine the optimal maximum follicular size (MFS) that will be adequate before the use of human chorionic gonadotropin trigger to induce ovulation. None of these studies have considered the woman's age as a factor. An in vitro fertilization-based study has also shown that large leading follicles did not result in higher percentage of matured oocytes, and they even result in a lower live birth rate; however, we note that the ages of the women were not specifically mentioned in connection with the problems of large follicle. Subjects and

Methods: We set out in this study to evaluate the relationship between the MFS and the woman's age both in our control group (fertile women) Group (A) and in the women attending fertility clinic Group (B). Using the Creighton Model Fertility Care System and NaProTECHNOLOGY, it was possible to determine when to start follicular tracking and also determine ultrasound diagnosis of ovulation by recording the MFS and the reduced size.

Results: In both Group A and Group B, we discovered that the MFS reduces as woman's age increases. We also discovered that the average MFS in the Group B was higher for age compared with the Group A (P = 0.0043). There was also an association between these bigger follicles for age and low mid-luteal progesterone. This is probably the first study that describes the association of follicular size and woman's age and its possible link with ovulation defects. Recommendation: We have proposed that this phenomenon of large matured maximum follicle for age could be a contributory factor to infertility and miscarriages. We propose further studies to verify this hypothesis.

Conclusion: Despite the high percentage of complete rupturing of follicles in the AB cycles in the Group (B) there are very high proportion having low mid luteal (P+7) Progesterone. This may be due to pathologies associated with big follicles for woman's age. The E2/Pg ratio study in luteal phase strongly suggested that the women in Group (B) that may have fertility challenge are those in subgroup of AB in Group (B). Therefore matured follicular size should be considered with the woman's age. If the follicles grows bigger away from the range for a woman's age it may be the marker for infertility or reproductive health challenges.

The Nigerian Journal of General Practice


The Current State of Science in Natural Family Planning


Thyroxine replacement for subfertile women with euthyroid autoimmune thyroid disease or subclinical hypothyroidism

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Yasmin Sajjad

IVF Department. Burjeel hospital. Abu Dhabi. UAE; Department of Obstetrics, Gynaecology and Reproductive Medicine; Najda Street Abu Dhabi United Arab Emirates

Abstract:
BACKGROUND: Thyroid disease is the second most common endocrine disorder affecting women of reproductive age. Subclinical hypothyroidism is diagnosed by an elevated thyroid-stimulating hormone concentration with a normal concentration of free thyroxine hormone. Autoimmune thyroid disease (ATD) is diagnosed by the presence of thyroid autoantibodies, regardless of thyroid hormone levels. Thyroxine may be a useful treatment for subfertile women with these two specific types of thyroid disease for improving pregnancy outcomes during assisted reproduction.

OBJECTIVES: To evaluate the efficacy and harms of levothyroxine replacement in subfertile women with subclinical hypothyroidism or with normal thyroid function and thyroid autoimmunity (euthyroid autoimmune thyroid disease, or euthyroid ATD) undergoing assisted reproduction.

SEARCH

METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers together with reference checking and contact with study authors and experts in the field to identify studies. We searched for all published and unpublished randomised controlled trials (RCTs) comparing thyroxine with no treatment or placebo, without language restrictions, from inception to 8 April 2019, and in consultation with the Cochrane CGF Information Specialist. SELECTION CRITERIA: We included women undergoing assisted reproduction treatment, meaning both in vitro fertilisation and intracytoplasmic sperm injection, with a history of subfertility and with subclinical hypothyroidism or with euthyroid ATD. We excluded women with a previously known clinical hypothyroidism or already taking thyroxine or tri-iodothyronine. RCTs compared thyroxine (levothyroxine) with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary review outcomes were live birth and adverse events of thyroxine; our secondary outcomes were clinical pregnancy, multiple pregnancy and miscarriage.

MAIN RESULTS: The review included four studies with 820 women. The included studies were of overall low risk of bias. Using GRADE methodology, we assessed the quality of evidence for the primary outcomes of this review to be very low- to low-quality evidence. Evidence was downgraded for imprecision as it was based on single, small trials with wide confidence intervals (CI). We were able to include data from three of the four included studies.In one study of women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies (autoimmune disease), the evidence suggested that thyroxine replacement may have improved live birth rate (RR 2.13, 95% CI 1.07 to 4.21; 1 RCT, n = 64; low-quality evidence) and it may have led to similar miscarriage rates (RR 0.11, 95% CI 0.01 to 1.98; 1 RCT, n = 64; low-quality evidence). The evidence suggested that women with both subclinical hypothyroidism and positive or negative anti-TPO antibodies would have a 25% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 27% and 100%.In women with normal thyroid function and thyroid autoimmunity (euthyroid ATD), treatment with thyroxine replacement compared with placebo or no treatment may have led to similar live birth rates (risk ratio (RR) 1.04, 95% CI 0.83 to 1.29; 2 RCTs, number of participants (n) = 686; I(2) = 46%; low-quality evidence) and miscarriage rates (RR 0.83, 95% CI 0.47 to 1.46, 2 RCTs, n = 686, I(2) = 0%; low-quality evidence). The evidence suggested that women with normal thyroid function and thyroid autoimmunity would have a 31% chance of a live birth with placebo or no treatment, and that the chance of a live birth in these women using thyroxine would be between 26% and 40%.Adverse events were rarely reported. One RCT reported 0/32 in the thyroxine replacement group and 1/32 preterm births in the control group in women diagnosed with subclinical hypothyroidism and positive or negative anti-TPO antibodies. One RCT reported 21/300 preterm births in the thyroxine replacement group and 19/300 preterm births in the control group in women diagnosed with positive anti-TPO antibodies. None of the RCTs reported on other maternal pregnancy complications, foetal complications or adverse effects of thyroxine. AUTHORS'

CONCLUSIONS: We could draw no clear conclusions in this systematic review due to the very low to low quality of the evidence reported.

The Cochrane Database of Systematic Reviews


Short- and long-term effect of contraceptive methods on fecundity

Olof Lundberg

a NaturalCycles Nordic AB , Stockholm , Sweden.

Simon P Rowland

Natural Cycles USA Corp, New York, New York, USA.

James Trussell

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

Elina Berglund Scherwitzl

Natural Cycles Nordic AB, Stockholm, Sweden

Kristina Gemzell-Danielsson

Department of Women's and Children's Health, Karolinska institutet, SE-17177 Stockholm, Sweden.

Abstract:
Objective: The aim of the study was to compare the effect of previously used contraceptive methods on women's shortand long-term fecundity. Use of hormonal contraception (HC) was compared with the use of a contraceptive mobile application (app).

Methods: This real-life prospective observational study comprised 2874 women who were attempting to become pregnant using the Natural Cycles mobile app to monitor their fertility. The women registered to use the app between August 2014 and June 2016 with the intention of planning a pregnancy and had previously either used the same app to prevent pregnancy or had recently discontinued HC use. We calculated the average time to pregnancy (TTP) for all women who became pregnant during the study and performed Kaplan-Meier life-table analysis to examine the cumulative probabilities of pregnancy for all women in the study.

Results: The average TTP was 2.3 (95% confidence interval [CI] 2.1, 2.4) and 3.7 (95% CI 3.4, 3.9) cycles for women who had previously used Natural Cycles and HC, respectively. The time to reach 30% pregnancy probability for women previously on HC was 1.6 (95% CI 1.5, 1.8) times longer than for women previously using Natural Cycles. There was no significant difference in the 13 cycle cumulated pregnancy probability between the two groups.

Conclusion: The results show that fertility awareness-based methods of contraception increase short-term pregnancy rates relative to HC, but have no effect on long-term pregnancy rates.

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


Dietary carbohydrate restriction improves metabolic syndrome independent of  weight loss

Stephen D Phinney

Virta Health, San Francisco, California, USA.

Ronald M Krauss

Department of Atherosclerosis Research, Children's Hospital Oakland Research Institute, Oakland, California, USA.

Abstract:
BACKGROUND: Metabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.

METHODS: Individuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.

RESULTS: Despite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.

CONCLUSION: Consistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02918422.

FUNDING: Dairy Management Inc. and the Dutch Dairy Association.


Adolescent combined hormonal contraceptives and surgical repair of anterior cruciate tears: a risky recommendation based on an unproven causal relationship

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: A recent cross-sectional national USA registry of surgery to repair anterior cruciate ligament tears found that fewer adolescent women who reported using combined hormonal contraceptives (CHC) had the surgery. They reviewed a complex literature on ovarian steroidal relationships with connective tissues biology, physiology and clinical issues. They concluded, based on their data and that evidence shows the greatest gender imbalance for women's ACL injury during adolescence, that all adolescent athletic women should be treated with CHC to prevent ACL injury. We caution that this admonition is using association to imply causation, implies we understand the ovarian hormonal relationships with connective tissues while that remains unclear, the directive to use CHC in adolescent ignores the recent meta-analytic evidence that its use is associated with failure to achieve peak bone mass and that these authors have used erroneous inferential reasoning and ignored the other variables besides sex and age related to ACL injury and the convincing evidence that training strategies can prevent tears.


Cancer risk among children conceived by fertility treatment

Lihui Chen

Fujian Agriculture and Forestry University

Abstract: Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers. The overall risk estimates and corresponding 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Sixteen cohort and thirteen case-control studies were included. Results showed that children conceived by fertility treatment had significantly higher risk for developing overall cancer (relative risk [RR]: 1.16, 95% CI: 1.01, 1.32), haematological malignancies (RR: 1.39, 95% CI: 1.21, 1.60) and other solid tumours (RR: 1.57, 95% CI: 1.14, 2.16). For specific cancers, fertility treatment was associated with a significantly increased risk of leukaemia (RR: 1.31, 95% CI: 1.09, 1.57) and hepatic tumours (RR: 2.26, 95% CI: 1.32, 3.85). Sensitivity analysis validated evidence of the robustness of the findings. The results may demonstrate a possible association between fertility treatment and an increased risk of cancer among the offspring. However, the findings cannot say whether this increased risk is due to the subfertility itself or to the fertility treatment. Further research is needed to address the underlying mechanisms.


Spending at least 120 minutes a week in nature is associated with good health and  wellbeing

Abstract: Spending time in natural environments can benefit health and well-being, but exposure-response relationships are under-researched. We examined associations between recreational nature contact in the last seven days and self-reported health and well-being. Participants (n = 19,806) were drawn from the Monitor of Engagement with the Natural Environment Survey (2014/15-2015/16); weighted to be nationally representative. Weekly contact was categorised using 60 min blocks. Analyses controlled for residential greenspace and other neighbourhood and individual factors. Compared to no nature contact last week, the likelihood of reporting good health or high well-being became significantly greater with contact ≥120 mins (e.g. 120-179 mins: ORs [95%CIs]: Health = 1.59 [1.31-1.92]; Well-being = 1.23 [1.08-1.40]). Positive associations peaked between 200-300 mins per week with no further gain. The pattern was consistent across key groups including older adults and those with long-term health issues. It did not matter how 120 mins of contact a week was achieved (e.g. one long vs. several shorter visits/week). Prospective longitudinal and intervention studies are a critical next step in developing possible weekly nature exposure guidelines comparable to those for physical activity.


Isthmocele: an overview of diagnosis and treatment

Raquel Papandreus Dibi

Universidade Federal de Ciências da Saúde de Porto Alegre

Thaysa Guglieri Kremer

Universidade Federal do Rio Grande do Sul

Abstract: An isthmocele, a cesarean scar defect or uterine niche, is any indentation representing myometrial discontinuity or a triangular anechoic defect in the anterior uterine wall, with the base communicating to the uterine cavity, at the site of a previous cesarean section scar. It can be classified as a small or large defect, depending on the wall thickness of the myometrial deficiency. Although usually asymptomatic, its primary symptom is abnormal or postmenstrual bleeding, and chronic pelvic pain may also occur. Infertility, placenta accrete or praevia, scar dehiscence, uterine rupture, and cesarean scar ectopic pregnancy may also appear as complications of this condition. The risk factors of isthmocele proven to date include retroflexed uterus and multiple cesarean sections. Nevertheless, factors such as a lower position of cesarean section, incomplete closure of the hysterotomy, early adhesions of the uterine wall and a genetic predisposition may also contribute to the development of a niche. As there are no definitive criteria for diagnosing an isthmocele, several imaging methods can be used to assess the integrity of the uterine wall and thus diagnose an isthmocele. However, transvaginal ultrasound and saline infusion sonohysterography emerge as specific, sensitive and cost-effective methods to diagnose isthmocele. The treatment includes clinical or surgical management, depending on the size of the defect, the presence of symptoms, the presence of secondary infertility and plans of childbearing. Surgical management includes minimally invasive approaches with sparing techniques such as hysteroscopic, laparoscopic or transvaginal procedures according to the defect size.

Revista Da Associacao Medica Brasileira (1992)


Concentrations of bisphenol A and parabens in socks for infants and young children in Spain and their hormone-like activities

Abstract:
Background: Little information is available on the content of bisphenol A (BPA) and other endocrine-disrupting chemicals (EDCs) such as parabens in infant textiles and clothes.Objectives1) To determine the concentrations of BPA and parabens in socks for infants and young children purchased in Spain, 2) to assess the (anti-)estrogenicity and (anti-)androgenicity of extracts from the socks, and 3) to estimate dermal exposure doses to these chemicals.

Methods: Thirty-two pairs of socks for infants and young children (1-48 months) were purchased from 3 stores in Granada (Spain). Textile material was cut from the foot, toe, and leg of each sock (n = 96 samples) for chemical analysis. Hormone-like activities were determined in foot sections (n = 32 samples) by using the E-Screen assay for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity.

Results: BPA was present in 90.6% of samples at concentrations ranging from <0.70 to 3736 ng/g. BPA levels were around 25-fold higher in socks from store 1, which had a higher cotton content compared to stores 2 and 3. Ethyl-paraben was found in 100% of samples, followed by methyl-paraben (81.0%), and propyl-paraben (43.7%). No butyl-paraben was detected in any sample. Estrogenic activity was detected in 83.3% of socks from store 1 (range = 48.2-6051 pM E2eq/g) but in only three socks from stores 2 and 3. Anti-androgenic activity was detected in six of the 32 socks studied (range = 94.4-2989 μM Proceq/g), all from store 1. Estimated dermal exposure to BPA was higher from socks for children aged 36-48 months (median = 17.6 pg/kg/day), and dermal exposure to parabens was higher from socks for children aged 24-36 months (median = 0.60 pg/kg/day).

Discussion: This is the first report in Europe on the wide presence of BPA and parabens in socks marketed for infants and children. BPA appears to contribute to the hormone-like activity observed in sock extracts.


Factors in the Hospital Experience Associated with Postpartum Breastfeeding Success

Lisa H Gren

Department of Family and Preventive Medicine, University of Utah Health, Salt Lake City, Utah.

Abstract:
Introduction: Hospitals are in a unique position to promote, protect, and support breastfeeding. However, the association between in-hospital events and breastfeeding success within population-based samples has not been well studied.

Materials and Methods: A stratified (by education and birth weight) systematic sample of 5,770 mothers taking part in the Utah Pregnancy Risk Assessment Monitoring System, 2012-2015, were included. Mothers, 2-4 months postpartum, completed the 82-item questionnaire, including if they had ever breastfed their new baby, and if so, current breastfeeding status. Relationships between in-hospital experiences and breastfeeding termination and duration were evaluated via Poisson and Cox proportional hazard regression models, respectively, adjusting for other in-hospital experiences, maternal age, race/ethnicity, maternal education, marital status, smoking, physical activity, delivery method, pregnancy complications, and length of hospital stay.

Results: Of all, 94.4% of mothers self-reported breastfeeding initiation, of whom 18.8% had breastfed <2 months, having breastfed on average 3.2 weeks (standard error: 0.07). In fully adjusted models, mothers who reported receiving a pacifier, receiving formula, or had staff help them learn how to breastfeed had a higher prevalence of terminating breastfeeding before 2 months (adjusted prevalence ratio [aPR] = 1.13, 95% confidence interval [CI]: 0.97-1.32; aPR = 1.20, 95% CI: 1.07-1.36; and aPR = 1.25, 95% CI: 1.08-1.34). Conversely, mothers who reported starting and feeding only breast milk in the hospital and receiving a phone number to call for help with breastfeeding had a lower prevalence of breastfeeding termination before 2 months (aPR = 0.72, 95% CI: 0.61-0.86; aPR = 0.57, 95% CI: 0.51-0.64; and aPR = 0.91, 95% CI: 0.80-1.03). Adjusted Cox models showed similar direction of associations.

Conclusions: Encouraging mothers to exclusively breastfeed in the hospital, and reducing gift packs containing pacifiers and formula, may be key areas United States hospitals can focus on to increase breastfeeding success. Prospective assessment in other geographical regions is needed to corroborate these findings.

Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine


Preconception Vitamin D Status and Offspring Sex Ratio Among Women with Prior Pregnancy Loss (OR17-05-19)

Alexandra Purdue-Smithe

Eunice Kennedy Shriver National Institute of Child Health and Human Development


Caffeinated beverage intake and serum caffeine metabolites and risk of pregnancy loss

Abstract:
Objectives: The association between caffeine and pregnancy loss remains controversial due to limitations of prior studies such as relying on self-reported intake only, exposure measurement after clinical confirmation of pregnancy, and potential time-varying confounding by nausea/vomiting and lifestyle factors, which may be affected by prior caffeine exposure. Thus, our aim was to evaluate associations of preconception and early pregnancy serum caffeine, paraxanthine, and theobromine, self-reported intake of caffeinated beverages, and risk of pregnancy loss among 1228 reproductive-age women attempting pregnancy in the EAGeR trial during 2007–2011.

Methods: We estimated HRs and 95% CIs for any pregnancy loss, hCG loss (prior to ultrasound confirmation), and clinical loss (after ultrasound confirmation) according to caffeinated beverage intake and caffeine biomarkers measured at preconception and the 8(th) week of gestation using weighted adjusted Cox proportional hazards models.

Results: At preconception, 67%, 28%, and 9% of women reported any intake of caffeinated sodas, coffee, and tea, respectively. Preconception total caffeinated beverage intake of ≥3 vs. 0 cups/day was associated with 85% (95% CI: 1.18, 2.94) higher risk of any pregnancy loss, driven primarily by associations for hCG loss (HR: 2.88 (95% CI: 1.20, 6.91)). Caffeinated soda intake was associated with hCG loss (≥2 vs. 0.2 vs. ≤0.2 ng/mL) at preconception was strongly associated with hCG loss (HR: 4.51 (95% CI: 1.36, 14.91)). Serum caffeine, paraxanthine, and theobromine measured at the 8th week of gestation were not associated with risk of loss.

Conclusions: Collectively, these data suggest that caffeine intake prior to pregnancy may increase risk of pregnancy loss, particularly in early gestation. Funding Sources: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.


Transgenerational Effects of Endocrine-Disrupting Chemicals on Male and Female Reproduction

Abstract: Endocrine-disrupting chemicals are known to interfere with normal reproductive function and hormone signaling. Phthalates, bisphenol A, pesticides, and environmental contaminants such as polychlorinated biphenyls and dioxins are known endocrine-disrupting chemicals that have been shown to negatively affect both male and female reproduction. Exposure to these chemicals occurs on a daily basis owing to these compounds being found in plastics, personal care products, and pesticides. Recently, studies have shown that these chemicals may cause transgenerational effects on reproduction in both males and females. This is of concern because exposure to these chemicals prenatally or during adult life can negatively impact the reproductive health of future generations. This mini-review summarizes the endocrine-disrupting chemicals that humans are exposed to on a daily basis and what is known about the transgenerational effects that these chemicals may have on male and female reproduction.


Building an evidence base for IVF 'add-ons'


A Simple and Improved Predictor of Insulin Resistance Extracted From the Oral  Glucose Tolerance Test: The I0*G60

Yanara A Bernal

Reproductive Health Research Institute, Santiago, Chile

Ana M Salgado

Pontificia Universidad Católica de Chile

Abstract:
Objective: To evaluate the diagnostic performance of several biochemical predictors of insulin resistance (IR).
Design: A total of 90 nondiabetic subjects were tested with both the pancreatic suppression test (PST) and the oral glucose tolerance test (OGTT). Of them, 53 were non-insulin-resistant (NIR) subjects and the remaining 37 were insulin resistant subjects.

Results: All glucose and insulin values from the OGTT were positively correlated with the steady-state plasma glucose (SSPG) value of the PST. Among the OGTT values, basal insulin (I0) displayed a stronger correlation with SSPG (r = 0.604). Receiver operating characteristic analysis of the OGTT data demonstrated that I0 exhibited the highest area under the receiver operating characteristic curve (AUROC), compared with the rest of the OGTT data. However, the reduced sensitivity of this predictor precluded its clinical use.We then tested six potential predictors of IR derived from the OGTT values. Of them, the I0*G60 had a correlation coefficient of 0.697 with the SSPG and an AUROC of 0.867, surpassing the respective values of the traditional biochemical predictors of IR. Its cutoff predicting IR was >1110 mg/dL*μΙU/mL (>428 nM*pM), its sensitivity was 0.865, and its global accuracy was 0.822. We then selected the six best biochemical predictors of IR according to their posttest probability ratio. The order was as follows: I0*G60, ISI composite, AUC-Gl*In/', quantitative insulin sensitivity check index, homeostatic model assessment 1 (HOMA1), and HOMA2.

Conclusion: We conclude that the I0*G60 is a promising, inexpensive, and easily calculable predictor of IR that outperforms the predictive power of the traditional predictors of IR, including the insulin sensitivity index composite.


Rola położnej w terapii niepłodności metodą NaProTechnology


Pilot observational prospective cohort study on the use of a novel home-based  urinary pregnanediol 3-glucuronide (PDG) test to confirm ovulation when used as  adjunct to fertility awareness methods (FAMs) stage 1

Abstract:
Rationale: Ovulation confirmation is a fundamental component of the evaluation of infertility.

Purpose: To inform the design of a larger clinical trial to determine the effectiveness of a new home-based pregnanediol glucuronide (PDG) urine test to confirm ovulation when compared with the standard of serum progesterone.

Methods: In this observational prospective cohort study (single group assignment) in an urban setting (stage 1), a convenience sample of 25 women (aged 18-42 years) collected daily first morning urine for luteinisinghormone (LH), PDG and kept a daily record of their cervical mucus for one menstrual cycle. Serum progesterone levels were measured to confirm ovulation. Sensitivity and specificity were used as the main outcome measures. Estimation of number of ultrasound (US)-monitored cycles needed for a future study was done using an exact binomial CI approach.

Results: Recruitment over 3 months was achieved (n=28) primarily via natural fertility regulation social groups. With an attrition rate of 22%, specificity of the test was 100% for confirming ovulation. Sensitivity varied depending on whether a peak-fertility mucus day or a positive LH test was observed during the cycle (85%-88%). Fifty per cent of participants found the test results easy to determine. A total of 73 US-monitored cycles would be needed to offer a narrow CI between 95% and 100%.

Conclusion: This is first study to clinically evaluate this test when used as adjunct to the fertility awareness methods. While this pilot study was not powered to validate or test efficacy, it helped to provide information on power, recruitment and retention, acceptability of the procedures and ease of its use by the participants. Given this test had a preliminary result of 100% specificity, further research with a larger clinical trial (stage 2) is recommended to both improve this technology and incorporate additional approaches to confirm ovulation.

TRIAL REGISTRATION NUMBER: NCT03230084.


Predictors of imminent non-vertebral fracture in elderly women with osteoporosis, low bone mass, or a history of fracture, based on data from the population-based Canadian Multicentre Osteoporosis Study (CaMos)

Jonathan D Adachi, Claudie Berger, Rich Barron, Derek Weycker, Tassos P Anastassiades, K Shawn Davison, David A Hanley, George Ioannidis, Stuart A Jackson, Robert G Josse, Stephanie M Kaiser, Christopher S Kovacs, William D Leslie, Suzanne N Morin, Alexandra Papaioannou, Jerilynn C Prior, Erinda Shyta, Amanda Silvia, Tanveer Towheed, David Goltzman

Abstract:
Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting this population for therapy.
Purpose: Fracture risk assessment has focused on a long-term horizon and populations with a broad risk range. For elderly women with osteoporosis or low bone mass, or a history of fragility fractures ("high-risk women"), risk prediction over a shorter horizon may have greater clinical relevance.

Methods: A repeated-observations design and data from the Canadian Multicentre Osteoporosis Study were employed. Study population comprised women aged ≥ 65 years with T score (total hip, femoral neck, spine) ≤ - 1.0 or prior fracture. Hazard ratios (HR) for predictors of low-trauma non-vertebral fracture during 2-year follow-up were estimated using multivariable shared frailty model.

Results: The study population included 3228 women who contributed 5004 observations; 4.8% experienced low-trauma non-vertebral fracture during the 2-year follow-up. In bivariate analyses, important risk factors included age, back pain, history of falls, history of low-trauma fracture, physical function, health status, and total hip T score. In multivariable analyses, only four independent predictors were identified: falls in past 12 months (≥ 2 falls: HR = 1.9; 1 fall: HR = 1.5), low-trauma fracture in past 12 months (≥ 1 fracture: HR = 1.7), SF-36 physical component summary score (≤ 42.0: HR = 1.6), and total hip T score (≤ - 3.5: HR = 3.7; > - 3.5 to ≤ - 2.5: HR = 2.5; > - 2.5 to ≤ - 1: HR = 1.3).

Conclusions: Imminent risk of low-trauma non-vertebral fracture is elevated among high-risk women with a history of falls or low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to identifying and targeting this population for therapy.


Comparative Thermal Effects of J-Plasma, Monopolar, Argon, and Laser Electrosurgery in a Porcine Tissue Model

Abstract: INTRODUCTION: The objective of this study was to understand how J-Plasma (Bovie Medical Corporation, Clearwater, Florida) surgical energy compares to monopolar, argon beam, and CO2 laser devices in terms of depth of penetration and lateral thermal spread in a porcine tissue model. MATERIALS AND METHODS: Using a porcine animal model, we applied the thermal energy of the J-Plasma laser, Bovie Monopolar Pencil (Bovie Medical Corporation, Clearwater, Florida), argon beam coagulator, and CO2 laser to porcine small bowel, bladder, and peritoneal tissues at equivalent settings. Tissue was excised and sent to pathology for histologic evaluation. Primary outcome was depth of penetration and lateral thermal spread. RESULTS: When applied to peritoneum tissue, CO2 laser had the greatest lateral thermal spread at 2.99mm, while the argon beam had the lowest at just under 1.5mm. With regard to depth of penetration, the monopolar pencil had the highest while J-Plasma had the lowest. When applied to bladder tissue, the argon beam was associated with the greatest lateral thermal spread (3.1mm) as compared to the other three devices (all less than 1mm). In terms of depth of penetration of bladder tissue, J-Plasma again had the lowest value, while the monopolar pencil had the highest. When applied to small intestine tissue, the argon beam had the greatest lateral spread (3.51mm), while J-Plasma had the lowest (less than 1mm). Regarding depth of penetration of small intestine tissue, argon beam had the highest value at 1.8mm compared to the other three devices (all below 0.6mm). CONCLUSION: Consistent with our previous study, J-Plasma had minimal lateral and depth spread when applied to various tissue types. J-Plasma performed better or similar when compared to monopolar, argon beam, and laser electrosurgical devices. Further studies in-vivo are needed to evaluate safety and surgical application of the J-Plasma device.


Fertility Treatment 2017: Trends and Figures

Human Fertilisation and Embryology Authority


A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy

Coomarasamy A, Devall AJ, Cheed V, Harb H, Middleton LJ, Gallos ID, Williams H, Eapen AK, Roberts T, Ogwulu CC, Goranitis I, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Kriedt K, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingam N, Watkins L, Wykes C, Horne A, Jurkovic D

Abstract:
Background: Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.

Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.

Results: A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups.

Conclusions: Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).


Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture.
Introduction: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture.

Methods: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information.

Results: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time.

Conclusions: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.