Platelet Rich Plasma in Gynecology-Discovering Undiscovered-Review

Dominika Streit-Ciećkiewicz

nd Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland.

Magdalena Emilia Grzybowska

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

Abstract: Regenerative medicine combines elements of tissue engineering and molecular biology aiming to support the regeneration and repair processes of damaged tissues, cells and organs. The most commonly used preparation in regenerative medicine is platelet rich plasma (PRP) containing numerous growth factors present in platelet granularities. This therapy is increasingly used in various fields of medicine. This article is a review of literature on the use of PRP in gynecology and obstetrics. There is no doubt that the released growth factors and proteins have a beneficial effect on wound healing and regeneration processes. So far, its widest application is in reproductive medicine, especially in cases of thin endometrium, Asherman's syndrome, or premature ovarian failure (POF) but also in wound healing and lower urinary tract symptoms (LUTS), such as urinary incontinence or recurrent genitourinary fistula auxiliary treatment. Further research is, however, needed to confirm the effectiveness and the possibility of its application in many other disorders.


Menstrual Cycle-Associated Changes in Micronutrient Biomarkers Concentration: A Prospective Cohort Study

Abstract: To evaluate variations in micronutrient biomarker concentrations and deficiencies across the menstrual cycle in a cohort of healthy women. This prospective cohort study was conducted among healthy women of reproductive age living in the State College area, Pennsylvania, (n = 45). Data collection occurred at the early follicular phase, the late follicular phase, and the midluteal phase. Fasting blood samples were collected to measure micronutrient biomarkers. At the early follicular phase, the mean ± SD concentrations for zinc, copper, magnesium, and retinol were 81.8 ± 16.2 µg/dL, 80.1 ± 12.8 µg/dL, 17.9 ± 1.4 mg/L, and 39.4 ± 9.3 µg/dL, respectively. The geometric mean (95% CI) for manganese, iron and ferritin concentrations were 1.51 [1.21, 1.87] µg/L, 106.7 [90.8, 125.4] µg/dL, and 26.4 [20.5, 34.0] µg/L, respectively. Mean concentrations of zinc and magnesium declined by 6.6% (p = 0.009) and 4.6% (p < 0.001) from the early follicular phase to the midluteal phase, respectively. Other biomarkers remained relatively constant across the cycle. At the early follicular phase, the prevalence of low serum concentrations for zinc, copper, magnesium, manganese, iron, and ferritin was 22%, 7%, 29%, 13%, 14%, and 28%, respectively. Also, in early follicular phase, 36% had anemia, and 13% specifically had iron deficiency anemia. The prevalence of magnesium deficiency was significantly higher at the midluteal phase vs. the early follicular phase (p = 0.025). Our study suggests that while many micronutrient concentrations are relatively constant across the menstrual cycle in healthy women, zinc and magnesium decline, and the prevalence of magnesium deficiency increases. Supplemental data for this article is available online at.

Journal of the American Nutrition Association


Antioxidants for male subfertility

Antioxidants for male subfertility

Abstract:
Background: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility.

Objectives: To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. SEARCH

Methods: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, and two trial registers were searched on 15 February 2021, together with reference checking and contact with experts in the field to identify additional trials.
Selection Criteria: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included men with idiopathic infertility and normal semen parameters or fertile men attending a fertility clinic because of female partner infertility.
Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes.

MAIN Results: We included 90 studies with a total population of 10,303 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing medically assisted reproduction (MAR). Investigators compared and combined 20 different oral antioxidants. The evidence was of 'low' to 'very low' certainty: the main limitation was that out of the 67 included studies in the meta-analysis only 20 studies reported clinical pregnancy, and of those 12 reported on live birth. The evidence is current up to February 2021. Live birth: antioxidants may lead to increased live birth rates (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.07 to 1.91, P = 0.02, 12 RCTs, 1283 men, I(2) = 44%, very low-certainty evidence). Results in the studies contributing to the analysis of live birth rate suggest that if the baseline chance of live birth following placebo or no treatment is assumed to be 16%, the chance following the use of antioxidants is estimated to be between 17% and 27%. However, this result was based on only 246 live births from 1283 couples in 12 small or medium-sized studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.22, 95% CI 0.85 to 1.75, 827 men, 8 RCTs, P = 0.27, I(2) = 32%). Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, P < 0.00001, 20 RCTs, 1706 men, I(2) = 3%, low-certainty evidence) compared with placebo or no treatment. This suggests that, in the studies contributing to the analysis of clinical pregnancy, if the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 15%, the chance following the use of antioxidants is estimated to be between 20% and 30%. This result was based on 327 clinical pregnancies from 1706 couples in 20 small studies. Adverse events Miscarriage: only six studies reported on this outcome and the event rate was very low. No evidence of a difference in miscarriage rate was found between the antioxidant and placebo or no treatment group (OR 1.46, 95% CI 0.75 to 2.83, P = 0.27, 6 RCTs, 664 men, I(2) = 35%, very low-certainty evidence). The findings suggest that in a population of subfertile couples, with male factor infertility, with an expected miscarriage rate of 5%, the risk of miscarriage following the use of an antioxidant would be between 4% and 13%. Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal discomfort when compared with placebo or no treatment (OR 2.70, 95% CI 1.46 to 4.99, P = 0.002, 16 RCTs, 1355 men, I(2) = 40%, low-certainty evidence). This suggests that if the chance of gastrointestinal discomfort following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 7%. However, this result was based on a low event rate of 46 out of 1355 men in 16 small or medium-sized studies, and the certainty of the evidence was rated low and heterogeneity was high. We were unable to draw conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. AUTHORS'

Conclusions: In this review, there is very low-certainty evidence from 12 small or medium-sized randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-certainty evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal discomfort, based on very low-certainty evidence. Subfertile couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials studying infertile men and reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.

The Cochrane Database of Systematic Reviews


The importance of nutrition in pregnancy and lactation: lifelong consequences

Abstract: Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.

American journal of obstetrics and gynecology


Uterine bleeding: how understanding endometrial physiology underpins menstrual health

Abstract: Menstruation is a physiological process that is typically uncomplicated. However, up to one third of women globally will be affected by abnormal uterine bleeding (AUB) at some point in their reproductive years. Menstruation (that is, endometrial shedding) is a fine balance between proliferation, decidualization, inflammation, hypoxia, apoptosis, haemostasis, vasoconstriction and, finally, repair and regeneration. An imbalance in any one of these processes can lead to the abnormal endometrial phenotype of AUB. Poor menstrual health has a negative impact on a person's physical, mental, social, emotional and financial well-being. On a global scale, iron deficiency and iron deficiency anaemia are closely linked with AUB, and are often under-reported and under-recognized. The International Federation of Gynecology and Obstetrics have produced standardized terminology and a classification system for the causes of AUB. This standardization will facilitate future research endeavours, diagnosis and clinical management. In a field where no new medications have been developed for over 20 years, emerging technologies are paving the way for a deeper understanding of the biology of the endometrium in health and disease, as well as opening up novel diagnostic and management avenues.


Inhibin-B and FSH Are Good Indicators of Spermatogenesis but Not the Best  Indicators of Fertility

Katarzyna Jankowska

Postgraduate School of Molecular Medicine

Piotr Dudek

Department of Endocrinology, Centre of Postgraduate Medical Education, ul. Cegłowska 80, 01-809 Warsaw, Poland.

Abstract: Biochemical markers of spermatogenesis and fertility assessment are important in the practical management of infertile males and the determination of an individual’s prognosis. We performed an analysis on 100 males with a male infertility factor. The following study inclusion parameters were analyzed: seminogram, FSH, LH, testosterone, estradiol, prolactin, TSH, and inhibin B concentrations. The patients were subsequently treated by reproductive endocrinologists in accordance with AUA/ASRM and EAU guidelines. The reproductive status was evaluated over a period of 3 years. We found a strong correlation of sperm count with inhibin B (r = 0.74, p < 0.001) and FSH concentration levels (r = −0.46, p < 0.001). Among 95 patients at follow-up, pregnancies occurred for 59 of their partners (48 spontaneous, 5 after IVF−ET, and 6 after IUI). Thirty-six patients remained childless despite the therapy. Sperm count and inhibin B level were the best predictors of natural fertilization (ROC AUC: 0.86 and 0.84; cut-off: 2.7 mln/mL and 45 pg/mL). Although inhibin B and FSH can be used to evaluate spermatogenesis and fertility, the initial sperm concentration appeared to be the best predictor of success. Pregnancy was achieved in a surprisingly large proportion of patients with a very low concentration of inhibin B and a low initial sperm count. It is noteworthy that 81% of the pregnancies were achieved without medically assisted reproduction.


Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome-A Review

Szabolcs Várbíró

Department of Obstetrics and Gynecology, Semmelweis University, 1182, Budapest, Üllői Út 78/A, Hungary. varbiro.szabolcs@med.semmelweis-univ.hu.

Abstract: Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.


Fate of Per- and Polyfluoroalkyl Substances from Durable Water-Repellent Clothing during Use

Abstract: To make outdoor clothing water- or dirt-repellent, durable water-repellent (DWR) coatings based on side-chain fluorinated polymers (SFPs) are used. During use of outdoor clothing, per- and polyfluoroalkyl substances (PFASs) can be emitted from the DWR to the environment. In this study, the effects of aging, washing, and tumble drying on the concentration of extractable PFASs in the DWR of perfluorohexane-based short-chain SFPs (FC-6 chemistry) and of perfluorooctane-based long-chain SFPs (FC-8 chemistry) were assessed. For this purpose, polyamide (PA) and polyester (PES) fabrics were coated with FC-6- and FC-8-based DWRs. Results show that aging of the coated fabrics causes an increase in concentration and formation of perfluoroalkyl acids (PFAAs). The effect of aging on the volatile PFASs depends on the type of fabric. Washing causes a decrease in PFAA concentrations, and in general, volatile PFASs are partly washed out of the textiles. However, washing can also increase the extractable concentration of volatile PFASs in the fabrics. This effect becomes stronger by a combination of aging and washing. Tumble drying does not affect the PFAS concentrations in textiles. In conclusion, aging and washing of fabrics coated with the DWR based on SFPs release PFASs to the environment.


Obstetric gaslighting and the denial of mothers' realities

Amelia Dmowska

University of California San Francisco and University of California Berkeley, United States.

Priya Fielding-Singh

Department of Family and Consumer Studies, University of Utah, 1527 E. Harvard Ave, Salt Lake City, UT, 84105, United States. Electronic address: priya.fielding-singh@fcs.utah.edu.

Abstract: Gaslighting is a type of abuse aimed at making victims question their sanity as well as the veracity and legitimacy of their own perspectives and feelings. In this article, we show how gaslighting can operate as a key, yet underexamined strategy of obstetric violence, or the institutional and interpersonal violation of women's rights during pregnancy, childbirth, and postpartum. We draw on forty-six in-depth, semi-structured interviews with mothers who experienced a traumatic childbirth to examine how obstetric providers gaslight mothers before, during and after childbirth when they deny - and thereby destabilize - mothers' realities. We identify and examine four core types of denials: denials of 1) mothers' humanity, 2) mothers' knowledge as valid, 3) mothers' judgements as rational and 4) mothers' feelings as legitimate. All four denials work to render mothers noncredible and their claims illegible within clinical encounters. In explicitly naming, theorizing, and examining obstetric gaslighting, our aims are threefold: 1) to uncover and theorize an underexamined mechanism of obstetric violence through a sociological lens, 2) to offer a typology of obstetric gaslighting's manifestations to aid scholars and practitioners in recognizing when obstetric gaslighting is occurring and 3) to advance a growing research program on gaslighting in medicine.


Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort

Eleonora Benhar

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

Jack T Pearson

Natural Cycles Nordic AB, Stockholm, Sweden

Abstract:
OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) vaccination is associated with changes in cycle or menses length in those receiving vaccination as compared with an unvaccinated cohort.

METHODS: We analyzed prospectively tracked menstrual cycle data using the application "Natural Cycles." We included U.S. residents aged 18-45 years with normal cycle lengths (24-38 days) for three consecutive cycles before the first vaccine dose followed by vaccine-dose cycles (cycles 4-6) or, if unvaccinated, six cycles over a similar time period. We calculated the mean within-individual change in cycle and menses length (three prevaccine cycles vs first- and second-dose cycles in the vaccinated cohort, and the first three cycles vs cycles four and five in the unvaccinated cohort). We used mixed-effects models to estimate the adjusted difference in change in cycle and menses length between the vaccinated and unvaccinated cohorts.

RESULTS: We included 3,959 individuals (vaccinated 2,403; unvaccinated 1,556). Most of the vaccinated cohort received the Pfizer-BioNTech vaccine (55%) (Moderna 35%, Johnson & Johnson/Janssen 7%). Overall, COVID-19 vaccine was associated with a less than 1-day change in cycle length for both vaccine-dose cycles compared with prevaccine cycles (first dose 0.71 day-increase, 98.75% CI 0.47-0.94; second dose 0.91, 98.75% CI 0.63-1.19); unvaccinated individuals saw no significant change compared with three baseline cycles (cycle four 0.07, 98.75% CI -0.22 to 0.35; cycle five 0.12, 98.75% CI -0.15 to 0.39). In adjusted models, the difference in change in cycle length between the vaccinated and unvaccinated cohorts was less than 1 day for both doses (difference in change: first dose 0.64 days, 98.75% CI 0.27-1.01; second dose 0.79 days, 98.75% CI 0.40-1.18). Change in menses length was not associated with vaccination.

CONCLUSION: Coronavirus disease 2019 (COVID-19) vaccination is associated with a small change in cycle length but not menses length.


Maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation

Abstract:
BACKGROUND: After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy.

OBJECTIVE: This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy.

STUDY DESIGN: This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity.

RESULTS: We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge.

CONCLUSION: Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.


Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome

Yue Cao

Affiliated Hospital of Southwest Medical University

Abstract: Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.


Preconception caffeine metabolites, caffeinated beverage intake, and fecundability

Keewan Kim

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Caffeine is the most frequently used psychoactive substance in the United States and >90% of reproductive-age women report some amount of intake daily. Despite biological plausibility, previous studies on caffeine and fecundability report conflicting results. Importantly, prior studies measured caffeine exposure exclusively by self-report, which is subject to measurement error and does not account for factors that influence caffeine metabolism.

Objectives: Our objective was to examine associations between preconception serum caffeine metabolites, caffeinated beverage intake, and fecundability.

Methods: Participants included 1228 women aged 18-40 y with a history of 1-2 pregnancy losses in the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial. We prospectively evaluated associations of preconception caffeine metabolites (i.e., caffeine, paraxanthine, and theobromine) measured from 1191 serum samples untimed to a specific time of day, self-reported usual caffeinated beverage intakes at baseline, and time-varying cycle-average caffeinated beverage intake, with fecundability. Using Cox proportional hazards models, we estimated fecundability odds ratios (FORs) and 95% CIs according to each metabolite. Follow-up was complete for 89% (n = 1088) of participants.

Results: At baseline, 85%, 73%, and 91% of women had detectable serum caffeine, paraxanthine, and theobromine, respectively. A total of 797 women became pregnant during ≤6 cycles of preconception follow-up. After adjusting for potential confounders, neither serum caffeine [tertile (T)3 compared with T1 For: 0.87; 95% CI: 0.71, 1.08], paraxanthine (T3 compared with T1 For: 0.92; 95% CI: 0.75, 1.14), nor theobromine (T3 compared with T1 For: 1.15; 95% CI: 0.95, 1.40) were associated with fecundability. Baseline intake of total caffeinated beverages was not associated with fecundability (>3 compared with 0 servings/d adjusted For: 0.99; 95% CI: 0.74, 1.34), nor was caffeinated coffee (>2 compared with 0 servings/d adjusted For: 0.93; 95% CI: 0.45, 1.92) or caffeinated soda (>2 servings/d adjusted For: 0.92; 95% CI: 0.71, 1.20).

Conclusions: Our findings are reassuring that caffeine exposure from usual low to moderate caffeinated beverage intake likely does not influence fecundability.This trial was registered at clinicaltrials.gov as NCT00467363.

The American journal of clinical nutrition


Fertility treatments and the risk of preterm birth among women with subfertility:  a linked-data retrospective cohort study

Abstract:
Background: In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women.

Methods: The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth.

Results: A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment.

Conclusion: IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.


Ovarian reserve parameters and IVF outcomes in 510 women with poor ovarian  response (POR) treated with intraovarian injection of autologous platelet rich  plasma (PRP)

Yigit Cakiroglu

Acibadem Maslak Hospital Assisted Reproductive Technologies Unit, Sariyer, Istanbul, Turkey

Abstract: The aim of the current study was to characterize ovarian reserve parameters and IVF outcomes in women with a history of poor ovarian response (POR) treated with intraovarian injection of autologous platelet rich plasma (PRP). Reproductive age women (N=510; age range 30-45yo) diagnosed with POR based on Poseidon criteria were included in the study. PRP treatment resulted in higher AFC, higher serum AMH, lower serum FSH, and a higher number of mature oocytes and cleavage and blastocyst stage embryos. After PRP injection, 22 women (4.3%) conceived spontaneously, 14 (2.7%) were lost to follow up, and 474 (92.9%) attempted IVF. Among women who attempted IVF, 312 (65.8%) generated embryos and underwent embryo transfer, 83 (17.5%) achieved a pregnancy, and 54 (11.4%) achieved sustained implantation/live birth (SI/LB). In total, of the 510 women with POR and mean age of 40.3, PRP resulted in improvement of ovarian reserve parameters, a pregnancy rate of 20.5% and SI/LB rate of 12.9%. Our findings suggest that PRP treatment may be considered in women with POR. For wider clinical application, its clinical efficacy will need to be demonstrated in prospective randomized clinical trials.


Association of infertility with atherosclerotic cardiovascular disease among  postmenopausal participants in the Women's Health Initiative

Robert A Wild

University of Oklahoma Health Sciences Center

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 -...

Abstract:
Objective: To investigate the association of infertility with atherosclerotic cardiovascular disease (ASCVD) among postmenopausal participants in the Women's Health Initiative (WHI). We hypothesized that nulliparity and pregnancy loss may reveal more extreme phenotypes of infertility, enabling further understanding of the association of infertility with ASCVD.
Design: Prospective cohort study.
Setting: Forty clinical centers in the United States. PATIENT(S): A total of 158,787 postmenopausal participants in the Women's Health Initiative cohort. INTERVENTION(S): Infertility, parity, and pregnancy loss. MAIN OUTCOME MEASURE(S): The primary outcome was risk of ASCVD among women with and without a history of infertility, stratified by history of live birth and pregnancy loss. Cox proportional-hazards models were adjusted for demographics and risk factors for ASCVD. RESULT(S): Among 158,787 women, 25,933 (16.3%) reported a history of infertility; 20,427 (80%) had at least 1 live birth; and 9,062 (35%) had at least 1 pregnancy loss. There was a moderate overall association between infertility and ASCVD (adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.99-1.06) over 19 years of follow-up. Among nulliparous women, infertility was associated with a 13% higher risk of ASCVD (95% CI, 1.04-1.23). Among nulliparous women who had a pregnancy loss, infertility was associated with a 36% higher risk of ASCVD (95% CI, 1.09-1.71). CONCLUSION(S): Women with a history of infertility overall had a moderately higher risk of ASCVD compared with women without a history of infertility. Atherosclerotic cardiovascular disease risk was much higher among nulliparous infertile women and among nulliparous infertile women who also had a pregnancy loss, suggesting that in these more extreme phenotypes, infertility may be associated with ASCVD risk.


Reply to: The Association Between Cognitive Decline and Bone Loss and Fracture Risk Is Not Affected by Medication With Anticholinergic Effect

Dana Bliuc, Thach Tran, Jonathan D Adachi, Gerald J Atkins, Claudie Berger, Joop van den Bergh, Roberto Cappai, John A Eisman, Tineke van Geel, Piet Geusens, David Goltzman, David A Hanley, Robert Josse, Stephanie Kaiser, Christopher S Kovacs, Lisa Langsetmo, Jerilynn C Prior, Tuan V Nguyen, Lucian B Solomon, Catherine Stapledon, Jacqueline R Center

Abstract: To the Editors: We are grateful to Dr. Naharci for the interest in our study reporting the association between cognitive decline and bone loss and fracture risk. (1) We agree that bisphosphonates (BPs) have a proven effect on reducing bone loss and fracture risk. (2) Medication with anticholinergic (ACH) side effects may also affect cogni-tive function as well as propensity to fall and fracture, although these effects have not been demonstrated in all studies. (3) We did not include these medication classes in our models because in observational studies the relationship between medication and outcomes is likely driven by factors associated with medication use. This bias by indication can only be avoided by specific study design (ie, propensity score matching), which was beyond the scope of our study. (4) However, we have conducted additional analyses to determine the prevalence of BP and ACH medication in our cohort, the association between these medication classes and our study outcomes and the impact of the addition of these medication classes to our findings. BP and ACH use were self-reported and obtained by questionnaire at baseline, and years 5 and 10. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) and cognitive function using the Mini Mental State Examination (MMSE) test during all clinical visits. Follow-up time for BMD


Study on Influencing Factors of Semen Quality in Fertile Men

Fang Lv

Second Affiliated Hospital of Soochow University

Meifang Song

Beijing Academy of Science and Technology

Cuige Shi

Department of Cell Biology, National Research Institute for Family Planning, Beijing, China.

Shucheng Zhang

Department of Health Quality Center, National Research Institute for Family Planning, Beijing, China.

Abstract:
Objective: To establish a system for evaluation of semen quality in fertile men by factor analysis (FA).

Methods: The FA method was used to analyze five sperm test indicators for fertile men (sperm pH, sperm motility, sperm progressive motility, semen density, and total sperm number) to determine the evaluation standard of semen quality. Pearson analysis was adopted for correlation testing.

Results: The comprehensive score formula for semen quality of normal fertile men was as follows: comprehensive score of semen quality = (0.38272 F(1) + 0.36359 F(2) + 0.20018 F (3))/94.699. Across the whole fertile population, semen quality was found to be correlated with abstinence period, age of first spermatorrhea, and frequency of intercourse. Smoking, drinking, and place of residence were correlated with semen quality in the high semen quality population. In the population with medium semen quality, only the abstinence period was associated with semen quality.

Conclusion: It is feasible to evaluate the semen quality of fertile men using the FA method. The comprehensive indicators of semen volume, sperm motility, and semen pH can be used as evaluative measures. Across the whole fertile population, the abstinence period and age of first spermatorrhea were correlated with semen quality. In the high semen quality population, smoking and drinking were negatively correlated with semen quality, and participants living in rural areas had better semen quality.


Psychiatric Symptoms Across the Menstrual Cycle in Adult Women: A Comprehensive  Review

Abstract: LEARNING Objective: After participating in this activity, learners should be better able to:• Discuss and outline the general and overlapping effects of the menstrual cycle on women's mental health. ABSTRACT: A growing body of research demonstrates menstrual cycle-dependent fluctuations in psychiatric symptoms; these fluctuations can therefore be considered as prevalent phenomena. Possible mechanisms underlying these fluctuations posit behavioral, psychological, and neuroendocrine influences. Recent reviews document cyclic exacerbation of symptoms and explore these mechanisms in the context of specific and often single disorders. The question remains, however, as to whether there are general and overlapping effects of the menstrual cycle on women's mental health. To address this gap, we synthesized the literature examining the exacerbation of a variety of psychiatric symptoms across the menstrual cycle in adult women. Results show that the premenstrual and menstrual phases are most consistently implicated in transdiagnostic symptom exacerbation. Specifically, strong evidence indicates increases in psychosis, mania, depression, suicide/suicide attempts, and alcohol use during these phases. Anxiety, stress, and binge eating appear to be elevated more generally throughout the luteal phase. The subjective effects of smoking and cocaine use are reduced during the luteal phase, but fewer data are available for other substances. Less consistent patterns are demonstrated for panic disorder, symptoms of posttraumatic stress disorder, and borderline personality disorder, and it is difficult to draw conclusions for symptoms of generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, and trichotillomania because of the limited data. Future research should focus on developing standardized approaches to identifying menstrual cycle phases and adapting pharmacological and behavioral interventions for managing fluctuations in psychiatric symptoms across the menstrual cycle.


Does scent attractiveness reveal women's ovulatory timing? Evidence from signal detection analyses and endocrine predictors of odour attractiveness

Abstract: Odour cues associated with shifts in ovarian hormones indicate ovulatory timing in females of many nonhuman species. Although prior evidence supports women's body odours smelling more attractive on days when conception is possible, that research has left ambiguous how diagnostic of ovulatory timing odour cues are, as well as whether shifts in odour attractiveness are correlated with shifts in ovarian hormones. Here, 46 women each provided six overnight scent and corresponding day saliva samples spaced five days apart, and completed luteinizing hormone tests to determine ovulatory timing. Scent samples collected near ovulation were rated more attractive, on average, relative to samples from the same women collected on other days. Importantly, however, signal detection analyses showed that rater discrimination of fertile window timing from odour attractiveness ratings was very poor. Within-women shifts in salivary oestradiol and progesterone were not significantly associated with within-women shifts in odour attractiveness. Between-women, mean oestradiol was positively associated with mean odour attractiveness. Our findings suggest that raters cannot reliably detect women's ovulatory timing from their scent attractiveness. The between-women effect of oestradiol raises the possibility that women's scents provide information about overall cycle fecundity, though further research is necessary to rigorously investigate this possibility.


Patient-Wise Methodology to Assess Glycemic Health Status: Applications to  Quantify the Efficacy and Physiological Targets of Polyphenols on Glycemic  Control

Sebastian Contreras

Max Planck Institute for Dynamics and Self-Organization

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia-which would have been missed with traditional binary diagnostic methods-enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.


Impact of progesterone on the gastrointestinal tract: a comprehensive literature review

Abstract: Women are more prone to gastrointestinal symptoms than men. A comprehensive literature search was performed to assess the impact of sex steroid hormone, especially progesterone, on the (healthy and diseased) gastrointestinal tract. Overall, 37 articles were identified. Based on these we conclude that progesterone has a dose-dependent and sex-dependent effect on gastric emptying (especially in mammals), slows down gastrointestinal motility, reduces the gallbladder's response to contractile stimulants, may support gastroesophageal reflux by reducing the esophageal sphincter pressure, may protect from Helicobacter pylori infection gastrointestinal sequelae (especially in mammals) and does not affect inflammatory bowel disease-specific symptoms. However, for several gastrointestinal symptoms and diseases no studies have yet been performed addressing the impact of sex hormone steroids.


Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes


Effects of hormonal contraceptives on dry eye disease: a population-based study

Abstract:
BACKGROUND: Hormonal contraceptives (HCs) are a known risk factor for dry eye disease (DED), yet the relationship between HCs use and DED in women of child-bearing age remains debatable. The aim of this study was to determine the association between HCs and DED in females of reproductive age.

METHODS: This was a retrospective cohort study using data from IQVIA's electronic medical record (IQVIA, USA). 4,871,504 women (age 15-45) between 2008 and 2018 were followed to the first diagnosis of DED as defined by an ICD-9/10 code. DED cases also required at least two prescriptions of cyclosporine or lifitegrast topical drops within 60 days of the first code. The date of the first code was designated as the index date. Regular HCs users needed to have at least two prescriptions in both the first year and second year prior to the index date. For each case, five controls were selected and matched to cases by age and follow-up time. A conditional logistic regression model was used to adjust for confounders of DED and to calculate odds ratios (ORs).

RESULTS: HCs users were at a higher risk for DED than non-users. Regular users of HCs were more likely to develop DED (ORs = 2.73, 95% CI [2.21-3.73]) than irregular users. Those who used a greater number of HCs were at a higher risk for DED.

CONCLUSIONS: This study indicates an increased risk of DED with HCs use in women of child-bearing age.


Primary Dysmenorrhea: Pathophysiology, Diagnosis, and Treatment Updates

Abstract: Primary dysmenorrhea (PD) is a common, disregarded, underdiagnosed, and inadequately treated complaint of both young and adult females. It is characterized by painful cramps in the lower abdomen, which start shortly before or at the onset of menses and which could last for 3 days. In particular, PD negatively impacts the quality of life (QOL) of young females and is the main reason behind their absenteeism from school or work. It is suggested that increased intrauterine secretion of prostaglandins F2α and E2 are responsible for the pelvic pain associated with this disorder. Its associated symptoms are physical and/or psychological. Its physical symptoms include headache, lethargy, sleep disturbances, tender breasts, various body pains, disturbed appetite, nausea, vomiting, constipation or diarrhea, and increased urination, whereas its psychological symptoms include mood disturbances, such as anxiety, depression, and irritability. While its diagnosis is based on patients' history, symptoms, and physical examination, its treatment aims to improve the QOL through the administration of nonsteroidal anti-inflammatory drugs, hormonal contraceptives, and/or the use of non-pharmacological aids (e.g., topical heat application and exercise). Patients must be monitored to measure their response to treatment, assess their adherence, observe potential side effects, and perform further investigations, if needed.


Periodontal disease and preterm delivery: a nationwide population-based cohort study of Taiwan

Dinh‐Toi Chu

Institute for Reproductive and Family Health

Abstract: Preterm delivery of low-birth weight infants is considered a leading cause of morbidity and mortality among neonates. Various studies have reported a positive correlation between periodontal disease (PD) and premature birth (PB) and yet no population-based study has assessed the impact of PD severity and treatments on premature birth. This cohort study used Taiwan's national medical records (1999-2012, included 1,757,774 pregnant women) to investigate the association between PD severity and PB. Women with PD during the 2-year period prior for giving birth were more likely to have PB (11.38%) than those without PD (10.56%; p < 0.001). After variables adjustment, the advanced PD group had OR of 1.09 (95% CI 1.07-1.11) for PB, the mild PD group had OR of 1.05 (95% CI 1.04-1.06), while no-PD group had OR of 1. Increased PD severity was related to higher risk of PB. When stratified by age, the highest ORs for PB were those aged from 31 to 35 years in both mild PD group (OR = 1.09, 95% CI 1.07-1.11) and advanced PD group (OR = 1.13, 95% CI 1.09-1.17). Improving periodontal health before or during pregnancy may prevent or reduce the occurrence of adverse pregnancy outcomes and therefore maternal and perinatal morbidity and mortality.


Prospective analyses of sex/gender-related publication decisions in general  medical journals: editorial rejection of population-based women's reproductive  physiology

Dharani Kalidasan

University of British Columbia, Vancouver, BC, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Objective: To assess whether editorial desk rejection at general medical journals (without peer review) of two clinical research manuscripts may relate to author gender or women's physiology topics. Given evidence for bias related to women in science and medicine, and editorial board attitudes, our hypothesis was that submissions by women authors, on women's reproductive, non-disease topics received differential editorial assessment.
Design: A prospective investigation of publications, author gender and topics in general medical journals in two issues following the editorial rejections of two clinical research manuscripts by five major English-language general medical journals. The rejected manuscripts (subsequently published in lower impact journals) described research funded by national granting bodies, in population-based samples, authored by well-published women scientists at accredited institutions and describing innovative women's reproductive physiology results.
Setting: Tertiary academic medical centre.

MAIN OUTCOME MEASURES: All clinical research published in the two issues following rejection date by each of the five major general medical journals were examined for first/senior author gender. The publication topic was assessed for its gendered population relevance, whether disease or physiology focused, and its funding. Rejection letters assessed editor gender and status.

Results: Women were underrepresented as original research authors; men were 84% of senior and 69% of first authors. There were no, non-disease focused publications relating to women's health, although most topics were relevant to both genders. The majority (80%) of rejection letters appeared to be written by junior-ranked women editors.

Conclusion: Sex/gender accountability is necessary for clinical research-based editorial decisions by major general medical journals. Suggestions to improve gender equity in general medical journal publication: (1) an editorial board sex/gender champion with power to advocate for manuscripts that are well-performed research of relevance to women's health/physiology; (2) an editorial rejection adjudication committee to review author challenges; and (3) gender parity in double-blind peer review.


An Outdoor Aging Study to Investigate the Release of Per- And Polyfluoroalkyl Substances (PFAS) from Functional Textiles

Abstract: The emission of per- and polyfluoroalkyl substances (PFAS) from functional textiles was investigated via an outdoor weathering experiment in Sydney, Australia. Polyamide (PA) textile fabrics treated with different water-repellent, side-chain fluorinated polymers (SFPs) were exposed on a rooftop to multiple natural stressors, including direct sunlight, precipitation, wind, and heat for 6-months. After weathering, additional stress was applied to the fabrics through abrasion and washing. Textile characterization using a multiplatform analytical approach revealed loss of both PFAS-containing textile fragments (e.g., microfibers) as well as formation and loss of low molecular weight PFAS, both of which occurred throughout weathering. These changes were accompanied by a loss of color and water repellency of the textile. The potential formation of perfluoroalkyl acids (PFAAs) from mobile residuals was quantified by oxidative conversion of extracts from unweathered textiles. Each SFP-textile finish emitted a distinct PFAA pattern following weathering, and in some cases the concentrations exceeded regulatory limits for textiles. In addition to transformation of residual low molecular weight PFAA-precursors, release of polymeric PFAS from degradation and loss of textile fibers/particles contributed to overall PFAS emissions during weathering.


Assessing the role of adolescent hormonal contraceptive use on risk for  depression: a 3-year longitudinal study protocol

Liisa A M Galea

Department of Psychology, University of British Columbia, Vancouver, Canada.

Frances S Chen

Department of Psychology University of British Columbia Vancouver BC Canada

Abstract:
Background: The incidence of depression in human females rises steadily throughout adolescence, a critical period of pubertal maturation marked by increasing levels of gonadal hormones including estrogens and progesterone. These gonadal hormones play a central role in social and emotional development and may also contribute to the increased occurrence of depression in females that begins in early adolescence. In this study, we examine whether and how introducing synthetic estrogen and progestin derivatives through the use of combined hormonal contraceptives (CHC), affects adolescent females' risk for developing depression. We further assess potential links between CHC use and alterations in stress responses and social-emotional functioning.

Methods: Using a longitudinal cohort design, we will follow a sample of adolescent females over the span of three years. Participants will be assessed at three time points: once when they are between 13 and 15 years of age, and at approximately 18 and 36 months after their initial assessment. Each time point will consist of two online sessions during which participants will complete a clinical interview that screens for key symptoms of mental health disorders, along with a series of questionnaires assessing their level of depressive symptoms and history of contraceptive use. They will also complete a standardized social-evaluative stress test and an emotion recognition task, as well as provide saliva samples to allow for assessment of their circulating free cortisol levels.

DISCUSSION: In this study we will assess the effect of CHC use during adolescence on development of Major Depressive Disorder (MDD). We will control for variables previously found to or proposed to partially account for the observed relationship between CHC use and MDD, including socioeconomic status, age of sexual debut, and CHC-related variables including age of first use, reasons for use, and its duration. In particular, we will discover whether CHC use increases depressive symptoms and/or MDD, whether elevated depressive symptoms and/or MDD predict a higher likelihood of starting CHC, or both. Furthermore, this study will allow us to clarify whether alterations in stress reactivity and social-emotional functioning serve as pathways through which CHC use may result in increased risk of depressive symptoms and/or MDD.


Fertility awareness and subclinical infertility among women trying to get pregnant at home

Abstract:
BACKGROUND: Recent studies on fertility awareness among the reproductive population have reported the lack of accurate knowledge about fertility and assisted reproductive technologies. However, there has been little information regarding women trying to get pregnant at home. The aim of this study was to explore the prevalence of subclinical infertility among women trying to get pregnant at home, and to evaluate awareness regarding infertility and reasons for not visiting infertility clinics among women who use pregnancy-assist mobile applications to help them conceive.

METHODS: A total of 2084 Japanese women responded to this online survey. We selected 1541 women according to the study criteria. Based on the results of 61 questions, we evaluated knowledge regarding fertility, prevalence of subclinical infertility, and reasons for not visiting the clinic among the participants.

RESULTS: Despite the desire to conceive, the participants had an apparent tendency to overestimate the age limit for childbearing. A total of 338 (21.9%) women answered that in general women aged > 45 years could get pregnant. Approximately 40% of the women had possible subclinical infertility and were unaware of the fact. Additionally, about 70% of the women considered themselves to have infertility problems. Women who were aware of the possibility of infertility hesitated to visit the clinic due to unfamiliarity with a gynecologist or clinic, and apprehensions about the gynecologic examination.

CONCLUSIONS: In our study, some women required treatment for infertility. Nonetheless, they hesitated to visit an infertility clinic. Sexual health education, together with proper accessibility to gynecology clinics, are necessary to reduce involuntary childlessness.


Assisted Reproductive Technology Surveillance - United States, 2018

Dmitry M. Kissin

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

Abstract: PROBLEM/CONDITION: Since the first US infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple births because multiple embryos might be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth, and low birthweight. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2018 and compares birth outcomes that occurred in 2018 (resulting from ART procedures performed in 2017 and 2018) with outcomes for all infants born in the United States in 2018. PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 US states, the District of Columbia, and Puerto Rico. RESULTS: In 2018, a total of 203,119 ART procedures (range: 196 in Alaska to 26,028 in California) were performed in 456 US fertility clinics and reported to CDC. These procedures resulted in 73,831 live-birth deliveries (range: 76 in Puerto Rico and Wyoming to 9,666 in California) and 81,478 infants born (range: 84 in Wyoming to 10,620 in California). Nationally, among women aged 15-44 years, the rate of ART procedures performed was 3,135 per 1 million women.


Optimization of Cervical Cancer Screening: A Stacking-Integrated Machine Learning Algorithm Based on Demographic, Behavioral, and Clinical Factors

Xiyao Liu

First Affiliated Hospital of Chongqing Medical University

Lei Sun

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Qi Zeng

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

Abstract:
Purpose: The purpose is to accurately identify women at high risk of developing cervical cancer so as to optimize cervical screening strategies and make better use of medical resources. However, the predictive models currently in use require clinical physiological and biochemical indicators, resulting in a smaller scope of application. Stacking-integrated machine learning (SIML) is an advanced machine learning technique that combined multiple learning algorithms to improve predictive performance. This study aimed to develop a stacking-integrated model that can be used to identify women at high risk of developing cervical cancer based on their demographic, behavioral, and historical clinical factors.

Methods: The data of 858 women screened for cervical cancer at a Venezuelan Hospital were used to develop the SIML algorithm. The screening data were randomly split into training data (80%) that were used to develop the algorithm and testing data (20%) that were used to validate the accuracy of the algorithms. The random forest (RF) model and univariate logistic regression were used to identify predictive features for developing cervical cancer. Twelve well-known ML algorithms were selected, and their performances in predicting cervical cancer were compared. A correlation coefficient matrix was used to cluster the models based on their performance. The SIML was then developed using the best-performing techniques. The sensitivity, specificity, and area under the curve (AUC) of all models were calculated.

Results: The RF model identified 18 features predictive of developing cervical cancer. The use of hormonal contraceptives was considered as the most important risk factor, followed by the number of pregnancies, years of smoking, and the number of sexual partners. The SIML algorithm had the best overall performance when compared with other methods and reached an AUC, sensitivity, and specificity of 0.877, 81.8%, and 81.9%, respectively.

Conclusion: This study shows that SIML can be used to accurately identify women at high risk of developing cervical cancer. This model could be used to personalize the screening program by optimizing the screening interval and care plan in highand low-risk patients based on their demographics, behavioral patterns, and clinical data.


Metabolic Syndrome among Patients with Polycystic Ovarian Syndrome Presenting to a Tertiary Care Hospital: A Descriptive Cross-Sectional Study

Anis Ahmad Chaudhary

Imam Mohammad ibn Saud Islamic University

Abstract:
INTRODUCTION: Metabolic syndrome in polycystic ovarian syndrome is associated with a long-term risk of developing type 2 diabetes mellitus and cardiovascular disease. This study aims to find the prevalence of metabolic syndrome among patients with polycystic ovarian syndrome presenting to a tertiary care hospital.

METHODS: A descriptive cross-sectional study was done on women attending the obstetrics and gynecology outpatient department of a tertiary care hospital from June 2020 to May 2021. A total of 106 women diagnosed with polycystic ovarian syndrome using Rotterdam criteria 2003 were recruited for the study and cases of metabolic syndrome was defined according to the modified American Heart Association/National Heart Lung and Blood Institute. Ethical approval was taken from the Institutional Review Committee of Nepal Medical College and Teaching Hospital (Reference number: 001-077/078). Convenience sampling was done. The collected data was entered and analyzed in Statistical Package for the Social Sciences version 21. Calculation of point estimate at 95% confidence interval was done along with frequency and proportion for binary data.

RESULTS: Among 106 women with polycystic ovarian syndrome, 50 (47.1%) had metabolic syndrome (37.59-56.60 at 95% Confidence Interval). The most common component of metabolic syndrome was low high-density lipoprotein cholesterol in 90 (84.9%) followed by central obesity in 60 (56.6%), hypertriglyceridemia in 47 (44.33%), high fasting sugar in 34 (32.07%), and high blood pressure in 14 (13.2%).

CONCLUSIONS: The prevalence of metabolic syndrome among patients with the polycystic ovarian syndrome was similar to other studies done in similar settings.

JNMA; journal of the Nepal Medical Association


Progesterone Actions and Resistance in Gynecological Disorders

Abstract: Estrogen and progesterone and their signaling mechanisms are tightly regulated to maintain a normal menstrual cycle and to support a successful pregnancy. The imbalance of estrogen and progesterone disrupts their complex regulatory mechanisms, leading to estrogen dominance and progesterone resistance. Gynecological diseases are heavily associated with dysregulated steroid hormones and can induce chronic pelvic pain, dysmenorrhea, dyspareunia, heavy bleeding, and infertility, which substantially impact the quality of women's lives. Because the menstrual cycle repeatably occurs during reproductive ages with dynamic changes and remodeling of reproductive-related tissues, these alterations can accumulate and induce chronic and recurrent conditions. This review focuses on faulty progesterone signaling mechanisms and cellular responses to progesterone in endometriosis, adenomyosis, leiomyoma (uterine fibroids), polycystic ovary syndrome (PCOS), and endometrial hyperplasia. We also summarize the association with gene mutations and steroid hormone regulation in disease progression as well as current hormonal therapies and the clinical consequences of progesterone resistance.


Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm  labour (the APRIL study): A multicentre, randomised, double-blinded,  placebo-controlled trial

Landman AJEMC, de Boer MA, Visser L, Nijman TAJ, Hemels MAC, Naaktgeboren CN, van der Weide MC, Mol BW, van Laar JOEH, Papatsonis DNM, Bekker MN, van Drongelen J, van Pampus MG, Sueters M, van der Ham DP, Sikkema JM, Zwart JJ, Huisjes AJM, van Huizen ME, Kleiverda G, Boon J, Franssen MTM, Hermes W, Visser H, de Groot CJM, Oudijk MA

Abstract:
Background: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. METHODS AND

Findings: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates.

Conclusions: In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth.

Trial Registration: Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.


Identifying dermal exposure as the dominant pathway of children's exposure to flame retardants in kindergartens

Zhaoyi Wang

Guangdong Province Women and Children Hospital

Abstract: Exploration of multiple sources of brominated (BFRs) and organophosphate flame retardants (OPFRs) for children promotes the understanding of exposure pathways and health risk. 10 BFRs and 9 OPFRs were measured in skin wipes from hands, forehead, and arms of 30 children, and surface wipe samples from sills, toys, desks and floors, and indoor air samples of kindergartens from Xinxiang, China. Higher ∑9OPFRs concentrations were observed in the forehead (1840 ng/m2), followed by hand (1420 ng/m2) and arm wipes (1130 ng/m2), and the ∑8BFRs concentrations in forehead, hand and arm wipes were 116, 315 and 165 ng/m2, respectively. The total concentration of OPFRs and BFRs in floor wipes (66.1 and 24.5 ng/m2) were lower than those in toy (205 and 535 ng/m2), sill (227 and 30.1 ng/m2) and desk (84.4 and 139 ng/m2) wipes. Concentrations of FRs in forehead wipes were significantly correlated with those in gaseous air (p < 0.05), moderate correlations were found between the hand wipes and surface wipes (p = 0.054). We estimated the daily average dosages (DADs) of children exposure to FRs via multiple pathways. Compared to DADs via inhalation and hand-to-mouth transfer, dermal exposure was determined to be the predominant exposure pathway to ∑9OPFRs and ∑8BFRs.


Multisite Effectiveness Study of the Marquette Method of Natural Family Planning Program

Abstract:
Women of reproductive age need reliable and effective family planning methods to manage their fertility. Natural family planning (NFP) methods or fertility awareness-based methods (FABMs) have been increasingly used by women due to their health benefits. Nevertheless, effectiveness of these natural methods remains inconsistent, and these methods are difficult for healthcare providers to implement in their clinical practice. The purpose of this study is to evaluate the effectiveness of the Marquette Model NFP system to avoid pregnancy for women at multiple teaching sites using twelve months of retrospectively collected teaching data. Survival analysis (Kaplan-Meier) was used to determine typical unintended pregnancy rates for a total of 1,221 women. There were forty-two unintended pregnancies which provided a typical use unintended pregnancy rate of 6.7 per 100 women over twelve months of use. Eleven of the forty-two unintended pregnancies were associated with correct use of the method. The total unintended pregnancy rate over twelve months of use was 2.8 per 100 for women with regular cycles, 8.0 per 100 women for the postpartum and breastfeeding women, and 4.3 per 100 for women with irregular menstrual cycles. The Marquette Model system of NFP was effective when provided by health professionals who completed the Marquette Model NFP teacher training program.
Summary: This study involved determining whether healthcare professionals at ten sites across the United States and Canada trained to provide the Marquette Method NFP services can replicate the effectiveness demonstrated in previous studies of the method. We found a high level of effectiveness (i.e., very low pregnancy rates) in using the Marquette Method among women from various regions across North America with diverse reproductive backgrounds and in particular when using hormonal fertility marker. Healthcare providers who have been trained to teach NFP can successfully incorporate NFP services in their practice and assist their clients in choosing appropriate family planning methods.


Use of contraceptives and risk of inflammatory bowel disease: a nested case-control study

Abstract:
BACKGROUND: How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described.

AIM: To examine associations between types of hormonal contraception and development of IBD.

METHODS: This was a nested case-control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated.

RESULTS: 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively).

CONCLUSIONS: We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.


Creatine as a Promising Component of Paternal Preconception Diet

Abstract: Male fertility has been declining globally over the past several decades, advancing from a personal issue to a public health problem. Beyond any doubt, a reduction in fertility (often characterized by low sperm count or motility) can severely threaten reproductive health and lifecourse framework in a long-term fashion. Aside from uncovering the currently unknown etiology of modern-day male infertility, the scientific and medical community faces a double burden: finding an efficient biomarker of impaired fertility and exploring any intervention that can act to enhance fertility. A plethora of nutritional compounds have been recognized as possible modulators of semen quality, and specific dietary patterns and nutrients appear to be accompanied by a lower risk of male infertility. Creatine, a conditionally essential nutrient, has caught attention as a male fertility-promoting candidate due to its role in sperm energy metabolism. This mini-review describes the creatine-related bioenergetics of spermatozoa, explores a connection between creatine levels and sperm quality in men, and critically examines available evidence for interventional studies with creatine to affect sperm viability.


The Impact of Oxidative Stress in Male Infertility

Maria Elisabetta Coccia

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

Abstract: At present infertility is affecting about 15% of couples and male factor is responsible for almost 50% of infertility cases. Oxidative stress, due to enhanced Reactive Oxygen Species (ROS) production and/or decreased antioxidants, has been repeatedly suggested as a new emerging causative factor of this condition. However, the central roles exerted by ROS in sperm physiology cannot be neglected. On these bases, the present review is focused on illustrating both the role of ROS in male infertility and their main sources of production. Oxidative stress assessment, the clinical use of redox biomarkers and the treatment of oxidative stress-related male infertility are also discussed.


Polycystic ovary syndrome and type 2 diabetes mellitus: A state-of-the-art review

Abstract: Polycystic ovary syndrome (PCOS) often coexists with a wide spectrum of dysglycemic conditions, ranging from impaired glucose tolerance to type 2 diabetes mellitus (T2D), which occur to a greater extent compared to healthy body mass index-matched women. This concurrence of disorders is mainly attributed to common pathogenetic pathways linking the two entities, such as insulin resistance. However, due to methodological flaws in the available studies and the multifaceted nature of the syndrome, there has been substantial controversy as to the exact association between T2D and PCOS which has not yet been elucidated. The aim of this review is to present the best available evidence regarding the epidemiology of dysglycemia in PCOS, the unique pathophysiological mechanisms underlying the progression of dysglycemia, the most appropriate methods for assessing glycemic status and the risk factors for T2D development in this population, as well as T2D risk after transition to menopause. Proposals for application of a holistic approach to enable optimal management of T2D risk in PCOS are also provided. Specifically, adoption of a healthy lifestyle with adherence to improved dietary patterns, such the Mediterranean diet, avoidance of consumption of endocrine-disrupting foods and beverages, regular exercise, and the effect of certain medications, such as metformin and glucagon-like peptide 1 receptor agonists, are discussed. Furthermore, the maintenance of a healthy weight is highlighted as a key factor in achievement of a significant reduction of T2D risk in women with PCOS.


Resilience and psychosocial factors linked to symptom experience during the menopause transition for women living with HIV

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Rebecca Gormley

Department of Medicine, Division of Infectious Diseases, University of British Columbia (UBC), Vancouver, BC, Canada.

Melanie C M Murray

Oak Tree Clinic, BC Women's Hospital and Health Centre, 4500 Oak St, Vancouver, British Columbia V5Z 0A7, Canada; Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6...

Abstract:
Objective: Women living with HIV (WLWH) are commonly symptomatic during perimenopause and menopause (≥1 y without menstruation), however, little is known of risks for symptoms and their timing. We analyzed these unwanted experiences to inform care.

Methods: WLWH (≥40 y) in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study rated midlife experiences for seven symptoms and a symptom composite (from 0 to 21). Timing was categorized into four phases: i) perimenopause (flow in the last year), ii) 1-2 years from final menstrual period (FMP), iii) 2-5 years post-FMP; and iv) >5 years post-FMP. Resilience (standardized out of 100) was assessed based on Wagnild's Resilience Scale. Univariable/multivariable mixed effects linear regression assessed correlates of symptom intensity by composite score.

Results: Among 457 peri-/menopausal women mean age 54.7 (±6.6) over two time points (703 observations), 88% experienced ≥1 mild symptom; 75% were of moderate and 55% severe intensity. The most frequently reported symptoms were joint/muscle stiffness (67%), depressed mood (67%), and hot flashes (57%). After adjusting for reproductive phase, we found that women with greater resilience had fewer/lower intensity symptoms (symptom score 1.37 [2.30 to 0.44] lower; P = 0.004); those with depressive symptoms and recreational drug use (respectively) had more/higher intensity symptoms (scores 1.71 [0.61 to 2.82] [P = 0.002]; 2.89 [2.09 to 3.77] [P<0.001] higher). Symptoms were most intense in perimenopause and declined with increasing menopausal years (P = 0.03).

Conclusions: WLWH experiences a high burden of midlife symptoms, decreased by resilience and most intense during perimenopause. Unwanted experiences were linked to psychosocial and behavioral factors. These data encourage HIV providers to adopt a bio-psychosocial approach to midlife management.


Fertile window and biophysical biomarkers of cervical secretion in subfertile cycles: a look at biotechnology applied to NaProTechnology

José María Murcia Lora

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

Jorge Enrique Mejía

Engineering Department, University Central of Colombia, 110311 Bogotá, Colombia

Abstract:
Background: The principal objective of this study was to correlate biophysical properties of vaginal discharge present in the cervical mucus with the timing of the fertile window. In particular, we produce measures of the viscoelasticity of the cervical secretion using two methods. The first uses only the elasticity extracted from the Creighton Model Fertility Care System (CrMs) scale, calculated P-6 ovulation estimated day (OED) with respect to the peak day of the CrMs. The second uses a numerical method that takes into account the changes in viscoelasticity, but without reference to the peak day calculated using the CrMs model. Using both methods, twelve records were obtained from a single female subject.

Methods: The methodology used to evaluate the viscoelasticity factor was by measuring the approximate length in centimeters (cm) of the vaginal discharge of cervical discharge. For this, the scale of the stretching graph established by observing the stretching of CrMS was used, taking into account the previous 6 days at peak day P-6. The first method, which we termed CFW (Clinical Fertile Window), uses a measure based on the approximate length (cm) of the maximal stretchiness of the vaginal discharge. The second method we termed SFW (Software-CrMS/strectching) (Software-based Fertile Window).

Results: The fertile window was detected correctly in 100% of the cases using either method, and a correlation value of 0.71 was observed between the two methods.

Conclusions: We conclude that the assessment of viscoelasticity using SFW algorithm allowed in this pilot study to detect the fertile window and to describe the evolution pattern of cervical discharge throughout the fertile window. Our study provides support for the use of computational methods in detecting the fertile window, taking only into account the time evolution of the cervical discharge throughout the menstrual cycle.

Clinical and Experimental Obstetrics & Gynecology


Prevalence of ocular anomalies is increased in women with polycystic ovary  syndrome-exploration of association with PAX6 genotype

Abstract:
Background: Polycystic Ovarian Syndrome (PCOS), the most common reproductive endocrine disorder affecting premenopausal women, is frequently associated with central obesity and pancreatic β-cell dysfunction. Aniridia, a rare congenital eye disorder with haploinsufficiency of the PAX6 gene, was observed to co-occur with PCOS in a proband. This study investigates eye health and PAX6 genotypes of women with PCOS and controls.

Materials and Methods: This is a cross-sectional study of 203 premenopausal women (100 healthy controls, 103 with PCOS) conducted at an academic medical center in Vancouver, Canada. Ophthalmological exams and detailed medical histories were obtained from each participant. DNA extracted from saliva was Sanger-sequenced for the exons, intron-exon boundaries, and untranslated regions of PAX6.

Results: Women with PCOS had eye abnormalities, including abnormalities of the anterior segment, optic nerve, and retina, that were not observed in controls (p = 0.0002). Myopia prevalence was similar in both groups. Dry eye syndrome, by history, was markedly more prevalent in women with PCOS (22.3%) than controls (5%), p = 0.004. PAX6 genotype did not significantly differ between the two groups, nor was it associated with the greater prevalence of eye anomalies observed in women with PCOS.

Conclusion: This is the first study to systematically perform an ophthalmological examination in women with PCOS, who were found to have a higher prevalence of potentially serious eye health problems compared with controls. These data suggest that ophthalmological-metabolic-genetic connections in women with PCOS require further investigation. Confirmation of these data and increased attention to eye health in women with PCOS appears warranted.


Factors associated with contraceptive use among women living with HIV in Canada:  a controlled, cross-sectional study

Amber R Campbell

Women's Health Research Institute  Vancouver British Columbia Canada

Hélène C F Côté

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

Chelsea Elwood

Women's Health Research Institute, Vancouver, BC V6H 3N1, Canada.

Jason Brophy

Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.

for the CIHR team grant on Cellular Aging, H. I. V. Comorbidities in Women, Children (CARMA), (CIHR HIV Clinical Trials Network study 277)

Abstract:
Background: Multiple contraindications to combined hormonal contraceptives (CHC) use exist. The impact of these factors on contraceptive choice, particularly among women living with HIV (WLWH), is not well understood. We measured and compared the prevalence of contraceptive use and contraindications among WLWH and women not living with HIV (controls).

Methods: We examined cross-sectional survey and medical chart data from 83 WLWH and 62 controls, aged 16-49 and sexually active, from 2013-2017. We compared the age-adjusted prevalence and types of contraceptives used in the last month and the proportion of women with CHC contraindications, including drug interactions, medical comorbidities, and smoking at ≥ 35 years old. All WLWH received care at an interdisciplinary, women-centred HIV clinic.

Results: Compared to controls, WLWH were older (median [IQR)] 39 [34-43] vs 31 [23-41] years; p = 0.003), had less post-secondary education (37% vs 73%; p < 0.001), and more often had household income < $15,000/year (49% vs 30%; p = 0.006). WLWH trended to higher contraceptive prevalence than controls (80% vs 63%; p = 0.06 adjusted for age). Overall hormonal contraceptive use was similar. However, despite controlling for age, WLWH used CHC less (4% vs 18%; p = 0.006) than controls, and had more frequently undergone tubal ligation (12% vs 2%; p = 0.03). WLWH also experienced more CHC contraindications (54% vs 13%; p = 0.0001), including smoking at ≥ 35 years old (30% vs 6%; p = 0.0003) or a CHC-related drug interaction (all antiretroviral related) (25% vs 0%; p = 0.0001).

Conclusions: WLWH attending our interdisciplinary clinic used hormonal contraception at similar rates as controls, though with different types. Differences may reflect different distributions of CHC contraindications. CHC contraindications present barriers to accessing the full range of contraceptive choices for WLWH. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed, especially when care is provided without the benefit of an interdisciplinary women-centered healthcare team.


Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity

Abstract: Cannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.


Birth Outcomes of Neonates Exposed to Marijuana in Utero: A Systematic Review and Meta-analysis

Abstract:
IMPORTANCE: While some studies have found an association between marijuana use and adverse neonatal outcomes, results have not been consistent across all trials.

OBJECTIVE: To assess available data on neonatal outcomes in marijuana-exposed pregnancies.

DATA SOURCES: PubMed, Medline, ClinicalTrials.gov, Cochrane, Scopus, and Web of Science were searched from each database's inception until August 16, 2021.

STUDY SELECTION: All interventional and observational studies that included pregnant women who were exposed to marijuana compared with pregnant women who were not exposed to marijuana and that reported neonatal outcomes were included.

DATA EXTRACTION AND SYNTHESIS: Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Data were extracted by 2 authors for all outcomes, which were pooled using a random-effects model as mean difference or risk ratio (RR) and 95% CI. Data were analyzed from August through September 2021.

MAIN OUTCOMES AND MEASURES: All outcomes were formulated prior to data collection. Outcomes included incidence of birth weight less than 2500 g, small for gestational age (defined as less than the fifth percentile fetal weight for gestational age), rate of preterm delivery (defined as before 37 weeks' gestation), gestational age at time of delivery, birth weight, incidence of neonatal intensive care unit (NICU) admission, Apgar score at 1 minute, Apgar score at 5 minutes, incidence of an Apgar score less than 7 at 5 minutes, fetal head circumference, and fetal length.

RESULTS: Among 16 studies including 59 138 patients, there were significant increases in 7 adverse neonatal outcomes among women who were exposed to marijuana during pregnancy vs those who were not exposed during pregnancy. These included increased risk of birth weight less than 2500 g (RR, 2.06 [95% CI, 1.25 to 3.42]; P = .005), small for gestational age (RR, 1.61 [95% CI, 1.44 to 1.79]; P < .001), preterm delivery (RR, 1.28 [95% CI, 1.16 to 1.42]; P < .001), and NICU admission (RR, 1.38 [95% CI, 1.18 to 1.62]; P < .001), along with decreased mean birth weight (mean difference, -112.30 [95% CI, -167.19 to -57.41] g; P < .001), Apgar score at 1 minute (mean difference, -0.26 [95% CI, -0.43 to -0.09]; P = .002), and infant head circumference (mean difference, -0.34 [95% CI, -0.63 to -0.06] cm; P = .02).

CONCLUSIONS AND RELEVANCE: This study found that women exposed to marijuana in pregnancy were at a significantly increased risk of some adverse neonatal outcomes. These findings suggest that increasing awareness about these risks may be associated with improved outcomes.


Acute Behavior of Oxygen Consumption, Lactate Concentrations, and Energy  Expenditure During Resistance Training: Comparisons Among Three Intensities

Gustavo A João

Department of Exercise Physiology Laboratory, Metropolitanas Unidas College, São Paulo, Brazil.

Nelson Carvas Junior

Department of Evidence-Based Health, Brazilian Cochrane Center, University Federal de São Paulo, São Paulo, Brazil.

Carlos Augusto Kalva-Filho

Laboratory of Applied Sports Science, Institute of Physical Education and Sports, Federal University of Alagoas, Maceió, Alagoas, Brazil.

Abstract:
Purpose: This study aimed to compare the oxygen consumption, lactate concentrations, and energy expenditure using three different intensities during the resistance training sessions.

Methods: A total of 15 men (22.9 ± 2.61 years) experienced in resistance training underwent 3 sessions composed of 8 exercises (chest press, pec deck, squat, lat pull-down, biceps curl, triceps extension, hamstring curl, and crunch machine), which were applied in the same order. The weight lifted differed among the sessions [high session: 6 sets of 5 repetitions at 90% of 1-repetition maximum (1-RM); intermediary session: 3 sets of 10 repetitions at 75% of 1-RM; and low session: 2 sets of 15 repetitions at 60% of 1-RM]. The oxygen consumption (VO(2))-during and after (excess post-exercise oxygen consumption (EPOC)) the session, blood lactate concentration, and energy expenditure (i.e., the sum of aerobic and anaerobic contributions, respectively) were assessed.

Results: The VO2 significantly decreased in the function of the weight lifting (F ((2.28)) = 17.02; p < 0.01; ηG2 = 0.32). However, the aerobic contributions significantly increase in the function of the weight lifting (F ((2.28)) = 79.18; p < 0.01; ηG2 = 0.75). The anaerobic contributions were not different among the sessions (p > 0.05; ηG2 < 0.01). Thus, the total energy expenditure during the session (kcal) significantly increased in the function of the weight lifting (F ((2.28)) = 86.68; p < 0.01; ηG2 = 0.75). The energy expenditure expressed in time unit (kcal·min(-1)) was higher in low session than in high session (F ((2.28)) = 6.20; p < 0.01; ηG2 = 0.15).

Conclusion: The weight lifted during resistance training-induced different physiological responses, which induced higher energy expenditure per unit of time during the low session.


Catholic Approaches to Procreation and Infertility

Abstract: Infertility is a worldwide problem today. The more conventional approach of medicine would be to diagnose the causes and correct them, so that the fertility potential of the couple would permit them to conceive naturally. However, since the advance of Assisted Reproductive Technologies, it has become a lucrative industry that seek to help anyone to procure a child. Lately, natural procreative processes such as NaProTechnology have arisen that can restore couples’ fertility potential through proper diagnosis and treatment. The Catholic Church prefers these latter approaches not only because they are truer to the nature of medical practice, but because they are more consistent with a healthy vision of human sexuality, procreation, and marriage.