Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Abstract: Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.


Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics

Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, typically characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Lifestyle or diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine alterations, and obesity are among the risk factors that predispose females to PCOS. These factors might contribute to upsurging metabolic syndrome by causing hyperinsulinemia, oxidative stress, hyperandrogenism, impaired folliculogenesis, and irregular menstrual cycles. Dysbiosis of gut microbiota may play a pathogenic role in the development of PCOS. The restoration of gut microbiota by probiotics, prebiotics, or a fecal microbiota transplant (FMT) might serve as an innovative, efficient, and noninvasive way to prevent and mitigate PCOS. This review deliberates on the variety of risk factors potentially involved in the etiology, prevalence, and modulation of PCOS, in addition to plausible therapeutic interventions, including miRNA therapy and the eubiosis of gut microbiota, that may help treat and manage PCOS.


Synchronization of the ovulation and copulation timings increased the number of  in vivo fertilized oocytes in superovulated female mice

Abstract: The number of sperm that reaches the oocytes in mammalian species is limited. In mice, 8-10 oocytes are ovulated, a similar number of sperm reaches the oocytes, and nearly all oocytes are fertilized via natural mating. Meanwhile, our improved superovulation technique (ultrasuperovulation: administration of inhibin antiserum and equine chorionic gonadotropin [IASe]) produced 100 oocytes from a single female C57BL/6 mouse but resulted in only approximately 20 fertilized oocytes via mating. We hypothesized that sperm shortage in the ampulla might cause this low fertilization rate. Mice were mated in the proestrus stage or after hormone injection, but ovulation timing was not considered. In clinical application, the rhythm method supports fertilization by testing the ovulation period and synchronizing the ovulation and copulation timings. Therefore, this study examined the effects of ovulation and copulation timings on in vivo fertilization in female mice with IASe. Synchronization of the ovulation and copulation timings increased fertilization efficiency in female mice with ultrasuperovulation. The number of embryos obtained post ovulation was three times higher than that obtained pre ovulation. This study suggests that synchronized ovulation and copulation timings improve the efficiency of in vivo fertilization in IASe-treated female mice. This technique can be used to produce genetically modified mice and develop technologies for infertility treatment.


Diagnosis and management of isthmocele (Cesarean scar defect): a SWOT analysis

Luis Alonso Pacheco

Reproductive Surgery Unit, Centro Gutenberg, Malaga, Spain.

J A Dominguez

IERA (Instituto Extremeño de Reproducción Asistida)  Badajoz Spain

F Perez-Milan

Department of Obstetrics and Gynecology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Abstract: The purpose of this State-of-the-Art Review was to provide a strategic analysis, in terms of strengths, weaknesses, opportunities and threats (SWOT analysis), of the current evidence regarding the management of uterine isthmocele (Cesarean scar defect). Strengths include the fact that isthmocele can be diagnosed on two-dimensional transvaginal ultrasound, and that surgical repair may restore natural fertility potential and prevent secondary infertility, as well as reduce the risk of miscarriage and other obstetric complications. However, there is a lack of high-quality evidence regarding the best diagnostic method and criteria, as well as the potential benefits of surgical repair with respect to fertility. There is a need for experienced surgeons skilled in the various isthmocele repair techniques. Isthmocele repair does not prevent the need for Cesarean delivery in subsequent pregnancies. There is increasing awareness regarding the accuracy of transvaginal ultrasound in diagnosing isthmocele. This may lead to surgical correction and prevention of obstetric and perinatal complications in subsequent pregnancies, including Cesarean scar pregnancy. Regarding threats, the existence of different surgical techniques means that there is a risk of selecting an inadequate approach if the type of isthmocele and the patient's characteristics are not considered. There is a risk of overtreatment when asymptomatic defects are repaired surgically. Finally, there is an absence of cost-effectiveness analyses to justify routine repair. Thus, while there are many data suggesting that isthmocele has an adverse effect on both natural fertility and the outcome of assisted reproduction techniques, high-quality evidence to support surgical isthmocele repair in all asymptomatic patients desiring future fertility are lacking. There is increasing agreement to recommend hysteroscopic repair of isthmocele as a first-line approach as long as the residual myometrial thickness is at least 2.5-3.0 mm.

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International  Society of Ultrasound in Obstetrics and Gynecology


Influence of Vitamin D supplementation on reproductive outcomes of infertile patients: a systematic review and meta-analysis

Abstract:
BACKGROUND: Low vitamin D status has been associated with an increased risk for infertility. Recent evidence regarding the efficacy of vitamin D supplementation in improving reproductive outcomes is inconsistent. Therefore, this systematic review was conducted to investigate whether vitamin D supplementation could improve the reproductive outcomes of infertile patients and evaluate how the parameters of vitamin D supplementation affected the clinical pregnancy rate.

METHODS: We searched seven electronic databases (CNKI, Cqvip, Wanfang, PubMed, Medline, Embase, and Cochrane Library) up to March 2022. Randomized and cohort studies were collected to assess the reproductive outcomes difference between the intervention (vitamin D) vs. the control (placebo or none). Mantel-Haenszel random effects models were used. Effects were reported as odds ratio (OR) and their 95% confidence interval (CI). PROSPERO database registration number: CRD42022304018.

RESULTS: Twelve eligible studies (n = 2352) were included: 9 randomized controlled trials (RCTs, n = 1677) and 3 cohort studies (n = 675). Pooled results indicated that infertile women treated with vitamin D had a significantly increased clinical pregnancy rate compared with the control group (OR: 1.70, 95% CI: 1.24-2.34; I2 = 63%, P = 0.001). However, the implantation, biochemical pregnancy, miscarriage, and multiple pregnancy rates had no significant difference (OR: 1.86, 95% CI: 1.00-3.47; I2 = 85%, P = 0.05; OR: 1.49; 0.98-2.26; I2 = 63%, P = 0.06; OR: 0.98, 95% CI: 0.63-1.53; I2 = 0%, P = 0.94 and OR: 3.64, 95% CI: 0.58-11.98; I2 = 68%, P = 0.21). The improvement of clinical pregnancy rate in the intervention group was influenced by the vitamin D level of patients, drug type, the total vitamin D dosage, the duration, administration frequency, and daily dosage of vitamin D supplementation. The infertile women (vitamin D level < 30 ng/mL) treated with the multicomponent drugs including vitamin D (10,000-50,000 IU or 50,000-500,000 IU), or got vitamin D 1000-10,000 IU daily, lasting for 30-60 days could achieve better pregnancy outcome.

CONCLUSION: To the best of our knowledge, this is the first meta-analysis systematically investigated that moderate daily dosing of vitamin D supplementation could improve the clinical pregnancy rate of infertile women and reported the effects of vitamin D supplementation parameters on pregnancy outcomes. A larger sample size and high-quality RCTs are necessary to optimize the parameters of vitamin D supplementation to help more infertile patients benefit from this therapy.

Reproductive biology and endocrinology : RB&E


Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women

Arianne Y.K. Albert

Women's Health Research Institute Vancouver BC 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...

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

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...

CIHR Team on Cellular Aging, HIV Comorbidities in Women, Children (CARMA-Endo; CIHR CTN 277)

Abstract:
Objectives: We sought to better understand factors associated with ovarian aging in women with HIV (WWH).
Design: HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV.

Methods: We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders.

Results: WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women.

Conclusions: Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.


In vitro fertilization increases the odds of gestational diabetes: a nationwide register-based cohort study


Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study With Within-Sibship Analysis

Abstract:
BACKGROUND: Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown.

METHODS: Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country.

RESULTS: Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]).

CONCLUSIONS: Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.


Development of a nutrition screening tool to identify need for dietetic intervention in female infertility

Abstract:
BACKGROUND: One in seven couples are impacted by infertility in the UK, and female infertility is often associated with several health conditions impacted by nutrition. Despite many studies aimed at identifying the critical role of nutrition in infertility, there is currently no screening tool that identifies nutritional risk factors for infertility.

AIM: To propose a self-administered screening tool to identify women who would benefit from nutritional intervention to promote fertility.

METHODS: A narrative review was carried out to identify and summarise modifiable nutritional risk factors that can influence female fertility, including comorbidities that can influence nutrition intake, absorption, and metabolism.

KEY FINDINGS: A nutrition screening tool outlining modifiable nutrition risk factors potentially improving female fertility has been proposed, comprising of BMI, medical history and quality of diet and lifestyle which would aid in designing evidence based dietetic services for female infertility.

Journal of human nutrition and dietetics : the official journal of the British Dietetic Association


Gonadotropin-Releasing Hormone Antagonists-A New Hope in Endometriosis Treatment?

Abstract: Endometriosis is a chronic disease, in which endometrial-like tissue is found outside the uterine cavity. Lesions are typically located in the true pelvis but can be found, in addition to extragenital endometriosis, in the respiratory system, the diaphragm, the pleura or the pericardium. As the extrauterine endometrial lesions undergo the menstrual cycle, they cause many symptoms, including pain, and besides infertility, they all mostly affect the quality of the patient's life. Pharmacological management of endometriosis significantly increases in importance either as a first-line treatment or as a complementary therapy after surgery. Yet, current research on antagonists of the gonadotropin-releasing hormone (GnRH) has revealed their potential benefits in endometriosis treatment. Their mechanism of action is to down-regulate the hypothalamic-pituitary-gonadal axis and therefore induce a hypoestrogenic state. The resulting reduction of estrogen levels prevents disease progression and diminishes the recurrence rate after surgical removal of endometriosis. The present review summarizes recent reports of the role oral GnRH antagonists have as a significant treatment option for pain reduction in endometriosis patients.


Inositol is an effective and safe treatment in polycystic ovary syndrome: a  systematic review and meta-analysis of randomized controlled trials

Szabolcs Várbíró

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

Abstract:
Background: Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.

Objective: Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.

Methods: The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).

Results: Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).

Conclusion: Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.

Trial Registration: PROSPERO registration number: CRD42021283275.

Reproductive Biology and Endocrinology : RB&E


Prevalence of medically induced psychological trauma and its influence on women's  health

Abstract:
Objective: The aim of the present study was three-fold. One, to assess the prevalence of medical traumatization in outpatients of a gynecologic department; two, to analyze the relationship of medical traumatization with adverse childhood events; and three, to investigate the extent to which medical traumatization affects the health outcomes of woman.

Methods: Between January and September 2022, a prospective cross-sectional study recruited patients of a gynecologic outpatient clinic at St. Gallen Cantonal Hospital in Switzerland. Medical trauma was a self-reported item. The presence of adverse childhood events was assessed using the Childhood Trauma Questionnaire. The severity of post-traumatic stress was evaluated using the Impact of Event Scale Revised questionnaire.

Results: In total, 227 patients were recruited. Medical trauma was reported by 20% of the interviewees and it was strongly associated with obesity (A = 0.005). Undergoing surgery was most commonly the source of psychological distress (5.7%) followed by delivery (4.8%), pregnancy loss (4.8%), and cancer diagnosis (4.0%). Yet, fewer than 1% of the patients reached the threshold suggesting post-traumatic stress disorder.

Conclusions: We found no relationship between the medical trauma, adverse childhood events, cardiovascular disease, or substance abuse. The presence of medical trauma was associated with the patient's body mass index (calculated as weight in kilograms divided by the square of height in meters).

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


Evidence-Based Lifestyle Guidelines and Self-Management Strategies Utilized by Women with Polycystic Ovary Syndrome

Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, affecting 13% of reproductive-aged women. While lifestyle management is the first-line treatment for improving complications, women experience challenges with implementation. This cross-sectional study aims to identify the types and sources of dietary and physical activity (PA) interventions implemented by women with PCOS and understand how they use self-management strategies to support lifestyle change. An online questionnaire was disseminated via a consumer-based PCOS website (May 2015-2016). Women (n = 1167) were aged 18-45 years and primarily born within the United States (70%). A quarter or less of women (diet 25%, PA 14%) sought lifestyle advice from health professionals (medical clinicians or dietitians) compared to over half (diet 59%, PA 67%) using alternative sources, namely from online platforms. While only 33% and 16% of women reported following formal dietary or PA guidelines, respectively, 57% had implemented a 'special diet' to manage their condition, many of which were inconsistent with evidence-based practice in PCOS. Participants also displayed a low level of engagement with important self-management behaviors, including goal setting and positive self-talk. These findings suggest that online information may promote inaccurate and ineffective lifestyle advice and emphasize the need to increase engagement with qualified health professionals.


Effects of Near-Infrared Light on Well-Being and Health in Human Subjects with  Mild Sleep-Related Complaints: A Double-Blind, Randomized, Placebo-Controlled  Study

Michael R. Krames

Seaborough Life Science, 1098 XG Amsterdam, The Netherlands

Praveen R Arany

University at Buffalo, State University of New York

Pauline P Bollen

Chrono@Work B.V., 9743 AD Groningen, The Netherlands

Michael S Kramer

Department of Pediatrics, McGill University Faculty of Medicine, Montreal, Quebec, Canada.

Abstract: Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm(-2)) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm(-2) to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.


What Do Social Media Influencers Say About Birth Control? A Content Analysis of  YouTube Vlogs About Birth Control

Abstract: Youth get their sexual health information from social media, often from social media influencers (SMIs) or microcelebrities with large followings. Previous research suggests that SMIs have powerful persuasive effects on attitudes and behaviors. Thus, it is important to examine the ways in which sexual health information, such as birth control, is conveyed by SMIs. Using framing theory as a theoretical framework, this study examines characteristics of SMIs and their shared experiences pertaining to birth control. A content analysis of YouTube vlogs (n = 50) posted from December 2019-2021 was conducted on SMIs who talk about their experiences using hormonal and non-hormonal birth control. SMI status was determined based on the number of people subscribed to the YouTube channels. Results suggest that SMI YouTube videos are primarily about the discontinuation of hormonal birth control and may provide inaccurate sexual health information. Reasons for discontinuation of hormonal birth control provided by the SMIs are discussed. Future research should explore the effects of influencer sexual health messaging on beliefs, attitudes, and behaviors.


Inequity of Access: Scoping the Barriers to Assisted Reproductive Technologies

Abstract: Infertility impacts millions of people of reproductive age worldwide, with approximately 10–15% of couples affected. When infertility is present, there are many potential barriers to treatment, leading to inequity of access. Assisted reproductive technologies (ART) are the mainstay of medical treatment for infertility and include procedures such as in vitro fertilisation. This scoping review aims to explore the barriers to accessing assisted reproductive technologies to highlight a potential role for the pharmacist in addressing these barriers. Five databases, including CINAHL, Emcare, Medline, Scopus, and Web of Science, were searched using keywords that resulted in 19 studies that explored barriers to initially accessing or continuing ART. Studies identified more than one barrier to accessing ART, with the most mentioned barrier being the geographic location of the patient, with others themed as psychological, financial, minority groups, educational level, and the age of the patient. Recommendations were made to address barriers to accessing ART, which included changes to government regulations to increase health education and promotion of infertility. Pharmacists’ accessibility, even in geographically remote locations, places them in an ideal position to address many of the challenges experienced by people accessing infertility treatment to improve outcomes for these people.


An Evaluation of US Medical Schools' Reproductive Health and Family Planning  Curricula

Abstract:
BACKGROUND AND Objectives: Knowledge and competency in the topics of reproductive health and family planning are important for primary care physicians. Given the high rates of unintended pregnancy, increasing rates of infertility and other gynecologic conditions, it is important for medical students, many of whom will become primary care physicians, to receive good foundational knowledge of reproductive health topics. The objective of this research project was to investigate the current curricula at US medical schools to determine the breadth and extent of education that medical students receive in reproductive health.

Methods: Medical students and faculty at 20 US medical schools shared all relevant materials from their required reproductive health curriculum used between 2016-2019, including syllabi, PowerPoint lectures, and official class handouts that were available to all students. From these, the number of mentions of 69 reproductive health-related terms were counted, including those related to family planning methods, abortion, ectopic pregnancy, reproductive counseling, and infertility.

Results: Of the over 9000 mentions of reproductive health terms, approximately half of mentions were related to family planning, with 10% related to abortion, 10% to infertility, and 6% to reproductive counseling. Family planning strategies emphasized oral contraceptives and long-acting reversible contraceptives with limited mentions of natural or fertility awareness-based methods.

Conclusions: This data demonstrates opportunities for broadening reproductive health education in medical school so that future primary care physicians are prepared to discuss the full range of reproductive options for their patients.


Sonographic diagnosis of adenomyosis-ultrasound that cried wolf?

Abstract: The presence of adenomyosis is traditionally confirmed by histopathologic examination of the uterine specimen. Today, it could be diagnosed by magnetic resonance imaging or ultrasound. Ultrasound diagnosis was previously less precise. However, with the advances in ultrasound technology including 3 dimensional ultrasound, the specificity and sensitivity of ultrasound to diagnose adenomyosis have increased. In addition, it has led to a clear increase in the prevalence of adenomyosis.


The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid

Dongyan Li

Second Hospital of Shanxi Medical University

Zhiqiang Zhang

Tianjin Medical University General Hospital

Yue Cao

Affiliated Hospital of Southwest Medical University

Abstract:
BACKGROUND: Endometriosis affects up to 10 % of women of reproductive age and can lead to infertility. Research investigating whether combined exposure to arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) is related to an increased risk of endometriosis, especially using different biological samples to validate the association, is very limited.

OBJECTIVE: This investigation aimed to evaluate the associations between the concentrations of As, Cd, Pb and Hg in blood and follicular fluid and the risk of endometriosis.

METHODS: A total of 609 endometriosis cases and controls seen at the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between April 2020 and December 2021 were included in our study. Blood (217 cases and 234 controls) and follicular fluid (182 cases and 203 controls) samples were collected from these subjects. The concentrations of Cd, Hg, As and Pb in the blood and follicular fluid were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were used to assess the associations between Cd, Hg, As or Pb levels and the risk of endometriosis; Bayesian kernel machine regression (BKMR) was used to evaluate the combined effect of metals on the risk of endometriosis.

RESULTS: We found significant associations between blood concentrations of As (highest vs. lowest tertile: aOR = 5.53, 95 % CI: 2.97, 10.30), Cd (second vs. lowest tertile: aOR = 1.96, 95 % CI: 1.07, 3.58; highest vs. lowest tertile: aOR = 3.21, 95 % CI: 1.79, 5.77), Pb (highest vs. lowest tertile: aOR = 2.73, 95 % CI: 1.56, 4.78) and Hg (high-level group vs. low-level group: aOR = 13.10, 95 % CI: 6.74, 25.44; second vs. lowest tertile: aOR = 15.27, 95 % CI: 4.96, 46.97; highest vs. lowest tertile: aOR = 35.66, 95 % CI: 11.99, 106.08) and increased risk of endometriosis adjusting for confounders. Follicular fluid As (highest vs. lowest tertile: aOR = 2.42, 95 % CI: 1.35, 4.33), Hg (highest vs. lowest tertile: aOR = 1.86, 95 % CI: 1.05, 3.29), Cd (second vs. lowest tertile: aOR = 2.45, 95 % CI: 1.29, 4.65; highest vs. lowest tertile: aOR = 3.12, 95 % CI: 1.67, 5.83), and Pb (second vs. lowest tertile: aOR = 1.97, 95 % CI: 1.11, 3.52) concentrations were positively associated with endometriosis risk. The BKMR analyses showed linear associations between the metal mixtures and the risk of endometriosis. Both in blood and in follicular fluid, As exhibited the highest contribution.

CONCLUSION: The data from this study suggest that toxic metals, individually and as a mixture, play a role in the risk of endometriosis, thus providing a novel idea for endometriosis prevention.


Vitamin D intakes among women living with and without HIV in Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

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...

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...

the CIHR team on Cellular Aging and HIV Comorbidities in Women and Children (CARMA)

Abstract:
Background: Patterns of vitamin D intake are relatively unexplored among women living with HIV, despite its importance for women's health. We compared vitamin D dietary and supplement intakes in women with HIV and population-based national controls and investigated barriers to intake.

Methods: In this case-control study, women with HIV in the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) cohort were matched with Canadian Multicentre Osteoporosis Study (CaMos) controls. Participants were queried for vitamin D in dairy consumption, supplementation/dosage, and sociodemographic variables. We assessed barriers to supplementation and factors associated with dietary intake by regression modelling.

Results: Ninety-five women living with HIV were age-matched to 284 controls. Women with HIV had lower income and bone mineral density and were more likely to smoke, take multiple medications and be non-white. Vitamin D dietary intake was lower in women living with HIV versus controls [0.76 vs. 1.79 μg/day; adjusted odds ratio (aOR) for greater than or equal to median intake 0.29 (0.12-0.61), p = 0.002], but any supplementation was higher [62.2% vs. 44.7%; aOR = 3.44 (95% CI: 1.16-11.00), p = 0.03]. Total vitamin D intake was similar between groups. Smoking was associated with no supplementation; non-white ethnicity and low income were related to lower dietary intake.

Conclusions: Women living with HIV showed lower dietary vitamin D intake but higher supplementation rates, suggesting that care providers are promoting supplementation. Women living with HIV who smoke, have low incomes and are non-white may particularly benefit from targeted efforts to improve vitamin D intake.


JSOG-ART Annual Report 2022 (体外受精・胚移植等の臨床実施成績 2022年)

Abstract: 日本産科婦人科学会 体外受精・胚移植等の臨床実施成績 2022年. ENGLISH SUMMARY: JSOG ART annual registry report for 2022 from the Japan Society of Obstetrics and Gynecology. Reports IVF, ICSI, and frozen-embryo-transfer cycle volumes and outcomes. Mandatory professional-society reporting from all JSOG-registered ART facilities in Japan.


Polycystic Ovarian Syndrome in Adolescents

Abstract: Polycystic ovarian syndrome (PCOS) is a metabolic, reproductive, and psychological complex series of disorders that impacts a woman throughout her lifespan. PCOS is a disorder of hormonal imbalance occurring in women of reproductive age. This disorder is characterized by high levels of male androgens like testosterone. This can lead to symptoms like irregular periods, amenorrhea (absence of menstruation), anovulation (absence of ovulation), hirsutism, acne, and obesity. PCOS also causes metabolic impairment. Multiple peripherally arranged immature follicles of about 2-5mm in diameter are present in the ovary. These follicles do not mature due to hormonal imbalances leading to an irregular menstrual cycle. PCOS is a metabolic, reproductive, and psychological complex series of disorders that impacts a woman throughout her lifespan. Polycystic ovarian syndrome is not a fatal or life-threatening disorder as its main complication is infertility. PCOS can be a root cause of serious medical conditions like obesity, hypertension, type-2 diabetes mellitus due to insulin resistance, endometrial cancers, ovarian cancer, etc. Stress may cause the hormone levels in the pituitary to fluctuate. Since the menstrual cycle is hormone-based, there are apparent irregularities.


RLA 2021 - Registro Latinoamericano de Reproduccion Asistida (Latin American Registry of Assisted Reproduction, treatment year 2021)

Abstract: REDLARA (Red Latinoamericana de Reproduccion Asistida) annual registry report for treatment year 2021. REDLARA is a voluntary multi-country aggregation of ART centres across 16 Latin American nations, covering approximately 75% of regional ART cycles. Reports IVF, ICSI, frozen embryo transfer, oocyte donation, and intrauterine insemination outcomes. From 2010 onward most annual reports were published as papers in JBRA Assisted Reproduction. Earlier reports (1990s and 2000s) were standalone Spanish-language print/PDF registry documents. Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Controlled ovarian stimulation in infertile women: a committee opinion

Practice Committee of the American Society for Reproductive Medicine


Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States

Abstract: The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.


Solvent-free automated thermal desorption-gas chromatography/mass spectrometry for direct screening of hazardous compounds in consumer textiles

Abstract:
AbstractThe global production of textiles utilizes numerous large-volume chemicals that may remain to some extent in the finished garments. Arylamines, quinolines, and halogenated nitrobenzene compounds are possible mutagens, carcinogens and/or skin sensitizers. For prevention, control of clothing and other textiles must be improved, especially those imported from countries without regulations of textile chemicals. An automated analytical methodology with on-line extraction, separation, and detection would largely simplify screening surveys of hazardous chemicals in textiles. Automated thermal desorption-gas chromatography/mass spectrometry (ATD-GC/MS) was developed and evaluated as a solvent-free, direct chemical analysis for screening of textiles. It requires a minimum of sample handling with a total run time of 38 min including sample desorption, chromatographic separation, and mass spectrometric detection. For most of the studied compounds, method quantification limit (MQL) was below 5 µg/g for 5 mg of textile sample, which is sufficiently low for screening and control of quinoline and arylamines regulated by EU. Several chemicals were detected and quantified when the ATD-GC/MS method was applied in a limited pilot screening of synthetic fiber garments. A number of arylamines were detected, where some of the halogenated dinitroanilines were found in concentrations up to 300 µg/g. This is ten times higher than the concentration limit for similar arylamines listed by the EU REACH regulation. Other chemicals detected in the investigated textiles were several quinolines, benzothiazole, naphthalene, and 3,5-dinitrobromobenzene. Based on the present results, we suggest ATD-GC/MS as a screening method for the control of harmful chemicals in clothing garments and other textiles.
                Graphical abstract


Recommendations from the 2023 international evidence-based guideline for the assessment and management of PCOS


Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series

Abstract: AbstractBackgroundThe textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM‐positive patients is DO 3. Around 85% of para‐phenylenediamine (PPD)‐allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD.ObjectivesTo study if DO 3 can be excluded from TDM 6.6%.MethodsPatch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet.ResultsContact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3‐positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%.ConclusionTDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.


Ethnic Diversity in Fertility Treatment 2021

Human Fertilisation and Embryology Authority

Abstract:
# Ethnic diversity in fertility treatment 2021
Preliminary UK ethnicity statistics for IVF and DI treatment, storage, and donation
Published: December 2023
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5rgnpqsr/ethnic-diversity-in-fertility-treatment-2021-underlying-dataset.xlsx "Ethnic diversity in fertility treatment 2021 - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#introduction)
- [Note on preliminary and ethnicity data](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#note-on-preliminary-and-ethnicity-data)
- [Section 1. IVF birth rates increased across all ethnic groups, though disparities remain](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-1)
- [Section 2. Black patients started fertility treatment later than other ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-2)
- [Section 3. DI predominantly used by White patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-3)
- [Section 4. Imported donor sperm and eggs vary by ethnicity](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-4)
- [Section 5. Multiple birth rate decreased in all ethnic groups, but remain highest for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2021/#section-5)
- [Section 6. Use of egg storage was similar across all ethnic groups](https://www.hfea.gov.uk/about-us/publications/res...


A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility

Chun-Pin Chang

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

Abstract:
INTRODUCTION: Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis.

METHODS: ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA).

RESULTS: Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation.

CONCLUSION: ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.


Endometriosis and cardiovascular disease: a population-based cohort study

Abstract:
BACKGROUND: Endometriosis, a prevalent condition among females of reproductive age, may be associated with increased risk of cardiovascular disease (CVD) through chronic inflammation and early menopause. The objective of this study was to estimate the association between endometriosis and subsequent risk of CVD.

METHODS: We conducted a population-based cohort study using administrative health data from Ontario residents from 1993 to 2015. We compared the incidence of CVD and cardiovascular health outcomes between females with endometriosis and 2 age-matched females without endometriosis. The primary outcome was hospital admission for CVD. Secondary outcomes included in-hospital CVD events of interest and emergency department visits for CVD. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) between endometriosis and CVD events.

RESULTS: We identified 166 835 eligible patients with endometriosis and matched 333 706 patients without endometriosis. The mean age of those with endometriosis was 36.4 years. Patients with endometriosis had a higher incidence of hospital admission for CVD (195 admissions/100 000 person-years) compared with those without endometriosis (163 admissions/100 000 person-years). Similarly, the incidence of secondary CVD events was slightly higher among patients with endometriosis (292 cases/100 000 person-years) than among those without endometriosis (224 cases/100 000 person-years). Females with endometriosis had an increased risk of hospital admission (adjusted HR 1.14, 95% confidence interval [CI] 1.10-1.19) and secondary CVD events (adjusted HR 1.26, 95% CI 1.23-1.30).

INTERPRETATION: In this large, population-based study, endometriosis was associated with a small increased risk of CVD events. Future studies need to investigate potential etiological mechanisms and strategies to decrease long-term CVD risk in patients with endometriosis.


Assisted reproductive technology in Japan: A summary report for 2020 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology

Abstract: Annual summary report on assisted reproductive technology (ART) cycles performed in Japan during 2020, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG).


Dynamic variation and inhalation exposure of organophosphates esters and phthalic acid esters in face masks

Caixia Wang

Second Affiliated Hospital of Zhejiang University

Abstract: The coronavirus pandemic (COVID-19) has posed a huge global health threat since December 2019. Wearing face masks is known as an effective measure for controlling the wide spread of COVID-19 and its variants. But on the other hand, face masks could be a potential source of organophosphate esters (OPEs) and phthalic acid esters (PAEs) as they are extensively added in masks. However, knowledge associated with the occurrence as well as inhalation risks of OPEs and PAEs in masks is limited. In this study, OPEs and PAEs were determined in different types of mask samples collected from the local market. OPEs and PAEs were detected in mask samples ranging from 36.7 to 855 ng/g, and from 251 to 3830 ng/g, respectively. Relatively lower OPEs and PAEs concentrations were observed in disposable mask for toddlers. Simulated inhalation experiment indicated that the mass loss of OPEs and PAEs was 136 and 3910 ng/mask in disposable masks, 71.9 and 763 ng/mask in disposable mask for toddlers, 924 and 1020 ng/mask in N95 mask after 12 h, respectively. Significantly negative correlations were exhibited between the decrement of OPEs in masks and the increment of OPEs in corresponding polyurethane foams (PUFs) during the course, elucidating OPEs released from masks could be well captured by PUFs. With regard to the variation over time, predominant OPE and PAE analogues showed semblable release and absorption tendency in mask and corresponding PUF. Inhalation exposure risk of OPEs and PAEs was estimated based on the increment of pollutants in PUF. The estimated daily intakes (EDIs), hazard index (HI) and carcinogenic risk (CR) were also calculated and they were within the threshold levels. This study provides the evidence of OPEs and PAEs releasing from the face masks during wearing and unveiled a potential source of OPEs and PAEs exposure to humans.


Previous induced abortion or miscarriage is associated with increased odds for gestational diabetes: a nationwide register-based cohort study in Finland

Abstract: AIMS: The aim of this study was to investigate the association between previous induced abortion or miscarriage and the development of gestational diabetes mellitus (GDM) using high-quality register data. METHODS: In this retrospective nationwide register-based cohort study, data from the national medical birth register (MBR) were used to evaluate the association between a history of miscarriage or induced abortion and GDM. We included all first pregnancies ending in delivery in which the oral glucose tolerance test was performed between 2004 and 2018. A logistic regression model was used to assess the development of GDM in the first pregnancy ending in delivery. Adjusted odds ratios (aOR) with 95% confidence intervals (Cis) were compared between groups. RESULTS: In total, 15,873 nulliparous women with a history of induced abortions, 22,337 with a history of miscarriages and 3594 with a history of both were found. The reference group consisted of 138,869 women without a history of induced abortions or miscarriages. Women with a history of induced abortions (24.7%, aOR 1.15 [CI 1.11-1.20]), a history of miscarriages (24.8%, aOR 1.14 [CI 1.10-1.18]) and a history of both (27.7% aOR 1.18 [CI 1.09-1.28]) had higher odds for the development of GDM when compared to the reference group (20.8%). The odds for GDM increased along with the increasing number of previous induced abortions and miscarriages. CONCLUSION: Women with a history of induced abortions or miscarriages had higher odds for GDM in their first pregnancy leading to birth. Knowledge of this association will be helpful in the prevention and screening of GDM.


Erratum: Is intracrinology of endometriosis relevant in clinical practice? A systematic review on estrogen metabolism


Rapport annuel d'AMP Vigilance 2022

Rapport annuel d'AMP Vigilance 2022

Abstract: Rapport annuel d'AMP Vigilance 2022 de l'Agence de la biomédecine. ENGLISH SUMMARY: 2022 ART adverse-event surveillance report from the French Agence de la biomédecine, covering serious adverse events and reactions in assisted reproduction during 2022.

Agence de la biomédecine - AMP Vigilance


Microfiber Emissions from Functionalized Textiles: Potential Threat for Human Health and Environmental Risks

Abstract: The growing worldwide population is directly responsible for the increased production and consumption of textile products. One of the key reasons for the generation of microfibers is the use of textiles and garment materials, which is expected to increase. The textile industry is responsible for the invisible pollution that is created by textile microfibers, which have been detected in marine sediments and organisms. The present review paper demonstrates that the microfibers discharged from functionalized textiles exhibit non-biodegradable characteristics and that a considerable proportion of them possess toxic properties. This is primarily attributed to the impact of textiles’ material functionalization on their biodegradability. The potential for these microfibers, which are released from textiles that contain a variety of dyes, toxic chemicals, and nanomaterials, to pose a variety of health risks to both humans and other living organisms is discussed in this paper. In addition, this paper covers a wide variety of preventative and minimizing measures for reduction, which are discussed in terms of several phases ranging from sustainable production through the consumer, end of life, domestic washing, and wastewater treatment phases.


Human Sexuality: Contemporary Lessons to be Learned

Karen Fredriksen-Goldsen

School of Social Work, University of Washington , Seattle, Washington , USA

Thomas W Hilgers

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


Morphologic alterations of the fear circuitry: the role of sex hormones and oral contraceptives

Abstract:
BACKGROUND: Endogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake.

OBJECTIVE: We investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network.

METHODS: We recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users' salivary ethinyl estradiol (EE) were assessed using liquid chromatography - tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods.

RESULTS: Compared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs.

DISCUSSION: Our results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.


Efficacy and safety of ondansetron for morning sickness in pregnancy: a systematic review of clinical trials

Abstract: Background: Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women suffer from morning sickness, a condition characterized by nausea and vomiting. However, it is still controversial regarding its safety during pregnancy, and continued research will be necessary to fully understand the risks and benefits associated with its use. Therefore, we aimed to identify and provide details of the efficacy and safety of ondansetron in clinical trials. Methods: A search was conducted of the ClinicalTrials.gov database on 13 April 2023, using the search term "ondansetron and pregnancy." Inclusion and exclusion criteria were defined to identify relevant clinical trials. The inclusion criteria encompassed clinical trials related to pregnancy that utilized ondansetron as a treatment, while other clinical trials were excluded from consideration. All data extractions such as study title, study status, study type, intervention details, and outcome were collected. Results: A total of 18 clinical trials were identified, of which only 6 focused on studying the effects of ondansetron. Their respective study titles, statuses, conditions, interventions, outcome measures, and enrollment sizes have been written in detail. The information collected from these trials will contribute to our understanding of the potential benefits and risks of ondansetron in the context of pregnancy and its complications. Conclusion: Ondansetron has been shown to be an effective treatment for nausea and vomiting, including pregnancy-related morning sickness. Further research is needed to better understand the potential risks and benefits associated with its use in pregnant women. Systematic Review Registration: ClinicalTrials.gov, identifier.


Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos

Abstract: Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.


CARTR Plus 2023 Plenary Slides - 2022 Data Summary

Abstract: CARTR Plus 2023 plenary slides presenting 2022 Canadian ART cycle data. Single-embryo transfer rates, clinical pregnancy and live-birth rates, ART-conceived births, and multiple-pregnancy rates by participating Canadian ART clinic.

Canadian Fertility and Andrology Society - CARTR Plus


Flame retardant textile finishing: thermal analysis and dermal security

Abstract: Many flame retardants (FRs) are brominated, and many of them are considered toxic, persistent and/or bio accumulative. A switch to non-halogenated alternatives for textile finishing is considered beneficial, but there is little knowledge about their environmental impact, their health risks during the production process and those in their final use.  A conventional and an alternative FR (based on dialkyl phosphono carboxylic acid amine and ammonium sulfamate; urea and organophosphonate PO(OH)2-R-PO(OH)2, respectively) were applied to cotton fabrics that could be in touch with the skin in their final use. Burning and thermal behaviors and dermal toxicity when exposed to skin rubbing are evaluated. Fabrics treated show that both FR products act as FRs. The increase in the thermal stability of the tissue that causes an increase in the decomposition temperature is a relevant effect associated with the application of the conventional FR in the tissue, while the most important effect of the alternative FR lies in the increase of the residue at 600°C, associated with the generation of fewer volatiles, which has an impact on the intensity of combustion. The study of the dermal toxic potential of FR-treated cotton bed sheets showed that the two tested products do not penetrate into the skin when applied under the conditions used and were safe when in contact with the skin. Moreover, the alternative FR seems to be safer when in contact with the skin considering also its higher concentration in the textile.


STORRM Registry Development Proposal: Systematic Tracking of Restorative Reproductive Medicine

International Institute for Restorative Reproductive Medicine


The prevalence and relevance of patch testing with textile dyes

Abstract: AbstractBackgroundTextile dye mix (TDM) is included in the European baseline series (EBS), but it is unknown if TDM identifies all patients with a textile dye allergy.ObjectivesTo assess the added value of performing patch testing with individual textile dyes in addition to TDM.MethodsTwo hundred and nine patients suspected to have a contact allergy to textile dyes were patch tested between January 2015 and December 2021 with the EBS, as well as an individual textile dye test series containing textile dyes part of TDM (TDM‐dyes) and outside the scope of TDM (non‐TDM dyes).ResultsFifty‐four patients (25.8%) tested positive for TDM or an individual textile dye. Disperse Orange 3 (9.6%) followed by Disperse Blue 106 (4.8%) were the most common individual textile dyes causing a positive patch test reaction. Of the 54 dye positive patients, 28 (51.9%) had a clinically relevant reaction. No clinically relevant reactions were seen in patients that solely tested positive for non‐TDM dyes.ConclusionsIt is beneficial to test individual textile dyes in addition to TDM in patients suspected of having a textile dye allergy. Otherwise, 46.3% of the dye positive patients and 35.7% of the patients with a clinically relevant reaction would have been missed.


ESHRE good practice recommendations on recurrent implantation failure

Nathalie Vermeulen

European Society of Human Reproduction and Embryology

Abstract:
Abstract

STUDY QUESTION
How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed?

SUMMARY ANSWER
This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy.

WHAT IS KNOWN ALREADY
RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit.

STUDY DESIGN, SIZE, DURATION
This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on ‘recurrent reproductive failure’, ‘recurrent implantation failure’, and ‘repeated implantation failure’.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received.

MAIN RESULTS AND THE ROLE OF CHANCE
The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: ‘RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were colour-coded based on whether the investigations/interventions were recommended (green), to be considered (orange), or not recommended, i.e. not to be offered routinely (red).

LIMITATIONS, REASONS FOR CAUTION
While awaiting the results of further studies and trials, the ESHRE Working Group on Recurrent Implantation Failure recommends identifying RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit.

WIDER IMPLICATIONS OF THE FINDINGS
This article provides not only good practice advice but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF.

STUDY FUNDING/COMPETING INTEREST(S)
The meetings and technical support for this project were funded by ESHRE. N.M. declared consulting fees from ArtPRED (The Netherlands) and Freya Biosciences (Denmark); Honoraria for lectures from Gedeon Richter, Merck, Abbott, and IBSA; being co-founder of Verso Biosense. He is Co-Chief Editor of Reproductive Biomedicine Online (RBMO). D.C. declared being an Associate Editor of Human Reproduction Update, and declared honoraria for lectures from Merck, Organon, IBSA, and Fairtility; support for attending meetings from Cooper Surgical, Fujifilm Irvine Scientific. G.G. declared that he or his institution received financial or non-financial support for re


Non-extractable PFAS in functional textiles—characterization by complementary methods: oxidation, hydrolysis, and fluorine sum parameters

Abstract: Oxidative methods (TOP and PhotoTOP) were combined with hydrolysis (THP assay) and fluorine sum parameters (EOF and TF) to characterize side-chain fluorinated polymers (SFPs) in functional textiles.


Rapport annuel d'activité 2022 - Agence de la biomédecine

Abstract: Rapport annuel d'activité 2022 de l'Agence de la biomédecine. Annual activity report covering Agence de la biomédecine activities including AMP (Medically Assisted Reproduction) registry operations for 2022.


Association between heavy metals exposure and infertility among American women aged 20-44 years: A cross-sectional analysis from 2013 to 2018 NHANES data

Junqiang Qiu

Ministry of Agriculture and Rural Affairs

Jing Xu

Second Affiliated Hospital of Zhejiang University

Abstract:
BACKGROUND: Infertility has been confirmed as a significant medical and social problem. Heavy metal exposure refers to a risk factor for infertility, which is capable of damaging the reproductive system of males and females. However, heavy metal exposure and female infertility have rarely been investigated. The aim of this study was to analyze the association between heavy metal exposure and female infertility.

METHODS: A cross-sectional study using data from three cycles of the National Health and Nutrition Examination Survey (NHANES, 2013-2018) was performed. Female infertility was evaluated by positive responses to question rhq074 in the questionnaire. Cadmium (Cd), lead (Pb), mercury (Hg), and arsenic (As) levels in blood or urine were examined by inductively coupled plasma mass spectrometry. The correlation between heavy metal and female infertility was analyzed through weighted logistic regression.

RESULTS: A total of 838 American women aged 20-44 years were covered in the study. Among all participants, 112 (13.37%) women were subjected to infertility. Urinary Cd and urinary As levels were significantly higher in infertile women than in control women (P < 0.05, P < 0.05). Urinary As showed a positive correlation with the prevalence of female infertility, and the risk of infertility rose with the increase of urinary As levels (P for trend = 0.045). Urinary Cd was associated with female infertility in some weighted logistic regression (Crude, Q2: OR = 3.99, 95% CI 1.82, 8.74, Q3: OR = 2.90, 95% CI 1.42, 5.92. Model 1, Q2: OR = 3.68, 95% CI 1.64, 8.27, Q3: OR = 2.33, 95% CI 1.13, 4.48. Model 2, Q2: OR = 4.11, 95% CI 1.63, 10.07, Q3: OR = 2.44, 95% CI 1.07, 5.53. Model 3, Q2: OR = 3.77, 95% CI 1.52, 9.35). Moreover, blood Pb (OR = 1.52, 95% CI 1.07, 2.16), urinary Pb (OR = 1.68, 95% CI 1.11, 2.55), and urinary As (OR = 1.02, 95% CI 1.00, 1.03) were positively correlated with the risk of infertility in women aged 35-44 years. The blood Pb (OR = 1.67, 95% CI 1.16, 2.40, 2.49) and urinary Pb (OR = 1.54, 95% CI 1.00, 2.38) in women with BMI ≥25 were positively correlated with the risk of infertility.

CONCLUSIONS: Urinary As was significantly associated with female infertility, and the risk of infertility increased with higher urinary As levels. To some extent, urinary Cd was correlated with infertility. Blood/urine Pb was related to infertility in advanced age and overweight/obese women. The results of this study need to be further validated in future prospective studies.


Outcome of Pregnancy by Status of Dominant Follicle as Evaluated by Ultrasound

Fong N

The Hong Kong Polytechnic University Faculty of Health and Social Sciences

Thomas W Hilgers

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


Role of Thyroid Hormone in Dynamic Variation of gdf6a Gene during Metamorphosis of Paralichthys olivaceus

International journal of molecular sciences


DIR Jahrbuch 2022 - Sonderausgabe für Paare (Patient Edition)

Abstract: DIR Jahrbuch 2022 Sonderausgabe für Paare des Deutschen IVF-Registers. ENGLISH SUMMARY: 2022 patient-facing edition of the German IVF Registry annual report. Translates clinical-registry data into accessible information for couples considering or undergoing ART in Germany, including success-rate context and treatment options.


Impact of textile dyes on human health and bioremediation of textile industry effluent using microorganisms

Abstract: AbstractEnvironmental contamination brought on by the discharge of wastewater from textile industries is a growing concern on a global scale. Textile industries produce a huge quantity of effluents containing a myriad of chemicals, mostly dyes. The discharge of such effluents into the aquatic environment results in pollution that adversely affects aquatic organisms. Synthetic dyes are complex aromatic chemical structures with carcinogenic and mutagenic properties in addition to high biological oxygen demand (BOD) and chemical oxygen demand (COD). This complex aromatic structure resists degradation by conventional techniques. The bioremediation approach is the biological clean-up of toxic contaminants from industrial effluents. Biological treatment methods produce less or no sludge and are cost-effective, efficient, and eco-friendly. Microorganisms, mostly microalgae and bacteria, and, in some instances, fungi, yeast, and enzymes decolorize textile dye compounds into simple, non-toxic chemical compounds. Following a thorough review of the literature, we are persuaded that microalgae and bacteria might be one of the potential decolorizing agents substituting for most other biological organisms in wastewater treatment. This article presents extensive literature information on textile dyes, their classification, the toxicity of dyes, and the bioremediation of toxic textile industry effluent utilizing microalgae and bacteria. Additionally, it combines data on factors influencing textile dye bioremediation, and a few suggestions for future research are proposed.


Impact of nutritional diet therapy on premenstrual syndrome

Abstract: Premenstrual syndrome (PMS) is one of the most common disorders faced by women of reproductive age. More than 200 symptoms of varying severity associated with PMS have been identified. Because of the broad spectrum of action of PMS and its impact on quality of life, symptom relief is the main challenge of treating PMS and premenstrual dysphoric disorder (PMDD). The review aims to analyze and identify the potential impact of dietary and nutritional therapies on PMS and, respectively, for its better management. The study was conducted by accessing Internet databases such as PubMed, ScienceDirect, and Scopus and using relevant keywords such as PMS, symptoms, dietary patterns (DPs), macro and micronutrients, and supplements. The results showed that diet is an essential modulating factor in reducing and managing PMS symptoms. But research on the actual effect of foods and nutrients on PMS is sparse, sporadic, and studied with insufficient scientific rigor. No correlations were identified between the consumption of macronutrients and PMS: protein, fat, carbohydrates, and fiber, but the effectiveness of micronutrients, especially calcium, magnesium, vitamin D, B vitamins, and herbal supplements, was demonstrated. Researchers remain unanimous that the evidence is insufficient and limited to support their use as an effective treatment. Nevertheless, the results could contribute to providing quality information to help women and girls make evidence-based decisions regarding premenstrual health and the adoption of dietary and nutritional therapies.


Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology


DIR Jahrbuch 2022 (Deutsches IVF-Register Annual Report 2022)

Abstract: DIR Jahrbuch 2022 des Deutschen IVF-Registers. ENGLISH SUMMARY: 2022 Annual Report of the German IVF Registry covering German ART cycle counts, treatment indications, embryo-transfer outcomes, and pregnancy/live-birth rates.


Cervical Mucus Anomalies in Patients with Endometriosis

Prachi D. Ruikar

Department Obstetrics & Gynecology Mamta Hospital (Dr. Ruikar), Latur, Maharashtra, India.

Rameshwari Alahabade

Department Obstetrics & Gynecology, Mamta Hospital (Dr. Alahabade), Latur, Maharashtra, India.

Rajashree Mahajan

Department Obstetrics & Gynecology, Mamta Hospital (Dr. Mahajan), Latur, Maharashtra, India.


Continuous Mucus in the Use of the Ovulation Method


Polycystic ovary syndrome and autoimmune thyroiditis

International Journal of Molecular Sciences


Nutrition in the prevention and treatment of endometriosis: A review

Abstract: Endometriosis is characterized by the presence of endometrial tissues outside the uterine lining, typically on the external surface of the uterus, the ovaries, fallopian tubes, abdominal wall, or intestines. The prevalence of endometriosis in North America, Australia, and Europe is \~1-5% in women of reproductive age. Treatment options for endometriosis are limited. While over-the-counter medications may be used to reduce acute pain, hormonal treatments are common and may interfere with fertility. In more severe cases, laparoscopic excision procedures and even hysterectomies are used to treat the pain associated with endometriosis. Nutritional interventions may be helpful in the prevention and treatment of endometriosis and associated pain. Reducing dietary fat and increasing dietary fiber have been shown to reduce circulating estrogen concentrations, suggesting a potential benefit for individuals with endometriosis, as it is an estrogen-dependent disease. Meat consumption is associated with greater risk of developing endometriosis. Anti-inflammatory properties of plant-based diets may benefit women with endometriosis. Additionally, seaweed holds estrogen-modulating properties that have benefitted postmenopausal women and offers potential to reduce estradiol concentrations in pre-menopausal women. Furthermore, consumption of vitamin D has been shown to reduce endometrial pain via increased antioxidant capacity and supplementation with vitamins C and E significantly reduced endometriosis symptoms, compared with placebo. More randomized clinical trials are needed to elucidate the role of diet in endometriosis.


Lifestyle, Insulin Resistance and Semen Quality as Co-Dependent Factors of Male Infertility

Abstract: Infertility is a problem that affects millions of couples around the world. It is known as a disease of couples, not individuals, which makes diagnosis difficult and treatment unclear. Male infertility can have many causes, from mechanical ones to abnormal spermatogenesis or spermiogenesis. Semen quality is determined by a number of factors, including those dependent on men themselves, with the number of infertile men growing every year. These include, e.g., diet, physical activity, sleep quality, stress, among many others. As these factors co-exist with insulin resistance, which is a disease closely related to lifestyle, it has been singled out in the study due to its role in affecting semen quality. In order to examine connections between lifestyle, insulin resistance, and semen quality, a review of literature published from 1989 to 2020 in the following databases PubMed/Medline, EMBASE (Elsevier), Scopus, Web of Science, and Google Scholar was performed. Hence, semen quality, environment, and insulin resistance are interrelated, thus it is difficult to indicate which aspect is the cause and which is the effect in a particular relationship and the nature of possible correlations. Since the influence of lifestyle on semen quality has been extensively studied, it is recommended that more thorough research be done on the relationship between insulin resistance and semen quality, comparing the semen quality of men with and without insulin resistance.

International journal of environmental research and public health


Breast cancer risk factors in Iranian women: a systematic review and  meta-analysis of matched case-control studies

Esmat-O-Sadat Hashemi

Academic Center for Education, Culture and Research

Masoud Solaymani-Dodaran

Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. msdodran@gmail.com.

Abstract:
Background: Identifying breast cancer risk factors is a critical component of preventative strategies for this disease. This study aims to identify modifiable and non-modifiable risk factors of breast cancer in Iranian women.

Methods: We used international databases (PubMed/Medline, Scopus, Web of Knowledge, and Embase) and national databases (SID, Magiran, and ISC) to retrieve relevant studies until November 13, 2022. The odds ratio (OR) with a 95% confidence interval using the random-effect model was used to estimate the pooled effect. The publication bias was assessed by the Egger and Begg test. A sensitivity analysis was conducted to evaluate the effect of each included study on the final measurement.

Results: Of the 30,351 retrieved articles, 24 matched case-control records were included with 12,460 participants (5675 newly diagnosed cases of breast cancer and 6785 control). This meta-analysis showed that of the known modifiable risk factors for breast cancer, obesity (vs normal weight) had the highest risk (OR = 2.17, 95% CI 1.47 to 3.21; I(2) = 85.7) followed by age at marriage (25-29 vs < 18 years old) (OR = 2.00, 95% CI 1.53 to 2.61; I(2) = 0), second-hand smoking (OR = 1.86, 95% CI 1.58 to 2.19; I(2) = 0), smoking (OR = 1.83, 95% CI 1.41 to 2.38; I(2) = 18.9), abortion history (OR = 1.44, 95% CI 1.02 to 2.05; I(2) = 66.3), oral contraceptive use (OR = 1.35, 95% CI 1.11 to 1.63; I(2) = 74.1), age at marriage (18-24 vs < 18 years old) (OR: 1.22, 95% CI 1.02 to 1.47; I(2) = 0). Of non-modifiable risk factors, history of radiation exposure (OR = 3.48, 95% CI 2.17 to 5.59; I(2) = 0), family history of breast cancer (OR = 2.47, 95% CI 1.83 to 3.33; I(2) = 73), and age at menarche (12-13 vs ≥ 14 years old) (OR = 1.67, 95% CI 1.31-2.13; I(2) = 25.4) significantly increased the risk of breast cancer.

Conclusions: Since most risk factors related to breast cancer incidence are modifiable, promoting healthy lifestyles can play an influential role in preventing breast cancer. In women with younger menarche age, a family history of breast cancer, or a history of radiation exposure, screening at short intervals is recommended.


Ovulation induction using sequential letrozole/gonadotrophin in infertile women  with PCOS: a randomized controlled trial

Abstract:
RESEARCH Question: Is sequential letrozole/human menopausal gonadotrophin (HMG) superior to letrozole alone in ovulation induction and pregnancy promotion among infertile women with polycystic ovary syndrome (PCOS)?
Design: This open-label randomized controlled trial comparing sequential letrozole/HMG and letrozole alone included 174 participants enrolled from August 2019 to January 2020 at the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology. Infertile women aged between 18 and 40 years who met Rotterdam criteria for PCOS and without other known causes of infertility were selected for this study. Patients were randomly assigned at a 1:1 ratio to receive 2.5 mg letrozole on cycle days 3-7 (n = 87) or 2.5 mg letrozole on cycle days 3-7 with a sequential injection of 75 IU HMG on cycle days 8-10 for one treatment cycle (n = 87). The pregnancy outcome was recorded after one treatment cycle.
Results: Women receiving sequential treatment achieved a significantly higher ovulation rate than those in the letrozole group (90.8% versus 70.1%, P = 0.001) and the live birth rate of the sequential group was significantly higher than that of the letrozole protocol (23.0% versus 10.3%, P = 0.025); there was no statistical variation with respect to adverse events.

Conclusions: The data suggest that the sequential letrozole/HMG protocol may be superior to the letrozole alone protocol in terms of ovulation induction and pregnancy promotion among infertile women with PCOS.


The Emerging Role of Menstrual-Blood-Derived Stem Cells in Endometriosis

Abstract: The human endometrium has a complex cellular composition that is capable of promoting cyclic regeneration, where endometrial stem cells play a critical role. Menstrual blood-derived stem cells (MenSC) were first discovered in 2007 and described as exhibiting mesenchymal stem cell properties, setting them in the spotlight for endometriosis research. The stem cell theory for endometriosis pathogenesis, supported by the consensual mechanism of retrograde menstruation, highlights the recognized importance that MenSC have gained by potentially being directly related to the genesis, development and maintenance of ectopic endometriotic lesions. Meanwhile, the differences observed between MenSC in patients with endometriosis and in healthy women underlines the applicability of these cells as a putative biomarker for the early diagnosis of endometriosis, as well as for the development of targeted therapies. It is expected that in the near future MenSC will have the potential to change the way we manage this complex disease, once their long-term safety and effectiveness are assessed.


Progestins in the symptomatic management of endometriosis: a meta-analysis on their effectiveness and safety

Abstract:
BACKGROUND: Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility.

METHOD & OUTCOME MEASURES: A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects.

RESULTS: Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = -0.61, 95% CI (-0.77, -0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6-12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 - 37.1%) with mild adverse effects reported.

CONCLUSION: The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021285026.


Sexual dysfunction among gynecologic cancer survivors in a population-based  cohort study

Chun-Pin Esther Chang

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

Chun-Pin Chang

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

Abstract: Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HR(Regional vs. Localized): 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.

Supportive Care in Cancer : Official Journal of the Multinational Association of  Supportive Care in Cancer


Assisted Reproductive Technology and Natural Law: How Seven Years as an  Embryologist Revealed IVF's Disordered Approach to Patient Care

Craig Turczynski

RRM Diagnostics, Dallas, TX, USA; Duquesne University College of Osteopathic Medicine, Pittsburgh, PA, USA

Mary Anne Urlakis

Dignitas Personae Institute for Nascent Human Life, Inc., Colgate, WI, USA

Abstract: This article is a case study illuminating the experience of a cradle Catholic who pursued a career in the field of Assisted Reproductive Technology (ART) as a laboratory director and embryologist. Twenty years after leaving the field, the observations leading to the crisis of conscience are further amplified by the reports of social, legal, ethical, and medical consequences of the technology. These consequences are explored in detail and can serve as a mini-review of the published scientific literature describing the obstetrical complications, peri-natal outcomes, and the long-term health effects on the offspring. This paper provides the documented evidence that can be used by the religious and medical community for shepherding the flock. The disordered approach to patient care is evidenced by five serious consequences resulting from the use of the technology. These include multiple pregnancy and selective reduction, abandoned and discarded embryos, adverse health effects to the women and children, legal and ethical problems, and human experimentation. An explanation for the adverse consequences can be found by exploring and applying the principles of Natural Law. Natural Law, as embraced by the Catholic Church, can be used as a starting point for conversion of heart for many who struggle with the immorality of ART. Deterring use of the technology coupled with increased motivation by scientist and health professionals to pursue restorative approaches within a moral framework offer our best solution to the treatment of infertility. Natural Law and the consequences of violating it provide evidence that science and medicine should not be practiced in a vacuum void of ethical and moral boundaries grounded in divine Wisdom.


Diagnosis and treatment of tubal endometriosis in women undergoing laparoscopy: A  case series from a single hospital

Abstract:
Background: Tubal endometriosis (TEM) is a category of pelvic endometriosis (EM) that is characterized by ectopic endometrial glands and/or stroma within any part of the fallopian tube. The fallopian tubes may be a partial source of ovarian endometriosis (OEM). TEM is difficult to diagnose during surgery and is usually detected by pathology after surgery.

Aim: To provide a clinical basis for the diagnosis and treatment of TEM.

Methods: In this study, the data of 30 patients who underwent laparoscopic salpingectomy due to various gynecological diseases and had pathological confirmation of TEM at our hospital were retrospectively analyzed, and the clinical basis for the diagnosis and treatment of TEM was evaluated.

Results: Among 1982 surgical patients, 30 met the study criteria. Among those, 6 patients had a history of infertility, 12 patients had a history of artificial abortion, 13 patients had a history of cesarean section, 1 patient had a history of tubal ligation, 4 patients had an intrauterine device, and 22 patients had hydrosalpinx. Sixteen patients (53.33%) conceived naturally and gave birth to healthy babies. Pathology showed that only 2 patients had TEM without any other gynecological diseases, while the others all had simultaneous diseases, including 26 patients with EM at other pelvic sites.

Conclusion: The final diagnosis of TEM depends on pathological examination since there are no specific clinical characteristics. The rate of TEM combined with EM (especially OEM) was higher than that of other gynecological diseases, which indicates that TEM is related to OEM.


Does a short luteal phase correlate with an increased risk of miscarriage? A  cohort study

Abstract:
Background: Miscarriage is defined as spontaneous loss of pregnancy prior to 20 weeks gestation. With an estimated risk of 15% of clinically confirmed pregnancies ending in miscarriage, it is the most common adverse event in pregnancy. Woman's age is the primary risk factor for miscarriage, while medical conditions, including hormonal abnormalities, are also associated. Progesterone is essential for maintaining pregnancy. A short luteal phase may reflect inadequate levels of progesterone production, but it is unclear whether a short luteal phase correlates with an increase in the risk of miscarriage.

Methods: Using a cohort study design, we conducted a secondary data analysis from four cohorts of couples who used a standardized protocol to track biomarkers of the female cycles. A short luteal phase was defined as less than 10 days, with < 11, < 9, and < 8 days as alternate definitions in sensitivity analyses. We included women who experienced a pregnancy with a known outcome, identified the length of the luteal phase in up to 3 cycles prior to conception and assessed the relationship with miscarriage using a modified Poisson regression analysis, adjusting for demographic characteristics, smoking, alcohol use and previous pregnancy history.

Results: In our sample of 252 women; the overall miscarriage rate was 18.7%. The adjusted incident risk ratio of miscarriage in women who had at least one short luteal phase < 10 days, compared to those who had none, was 1.01 (95% CI: 0.57, 1.80) Similar null risk was found when assessing alternative lengths of short luteal phase. Women who had short luteal phases < 10 days in all 3 cycles prior to the conception cycle had an incident risk ratio of 2.14 (95% CI: 0.7, 6.55).

Conclusions: Our study found that a short luteal phase in the three cycles prior to conception was not associated with higher rates of miscarriage in an international cohort of women tracking their cycles, but our sample size was limited. Further research to determine if short luteal phases or luteal phase deficiency is associated with early pregnancy losses among preconception cohorts with daily tracking of cycle parameters, in addition to progesterone and human chorionic gonadotropin levels, is warranted. Additionally, future studies should include women with recurrent short luteal phases as a more likely risk factor than isolated short luteal phases.


Impact of Endocrine Disorders on IVF Outcomes: Results from a Large,  Single-Centre, Prospective Study

Vito Chiantera

Unit of Gynecologic Oncology, ARNAS “Civico-Di Cristina-Benfratelli”, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Paler...

Abstract: Endocrine disorders negatively influence the ovarian function, and increasing incidence of endocrine diseases with age may have further negative effects on pregnancy rate. Prospective cohort study of 231 consecutively enrolled patients underwent IVF treatment. In patients with known endocrine disorders, the laboratory parameters were corrected before IVF treatment. One hundred sixty one patients (69.7%) had at least one known and treated endocrine disorder (study group), and 70 patients were endocrine negative (control group). Endocrine disorders diagnosed were thyroid disorders (32.5%), diminished ovarian reserve (23.8%), insulin resistance (22.5%), PCOS (15.2%), hyperprolactinaemia (13.4%), obesity (12.1%), hypogonadotropic hypogonadism (0.8%) and congenital adrenal hyperplasia (0.2%). Before the IVF treatment, systematic endocrine laboratory examinations were performed in all patients. Higher age, BMI and FSH were found in the study group, while AMH level was lower. There were no differences in LH, E2, prolactin, TSH, FT3, FT4, TT, DHEAS, androstendione, 17-OHP and SHBG level between the study and control groups. The study group had higher baseline glucose, baseline insulin, 120-min glucose and 120-min insulin level after oral glucose tolerance test. With no difference in the IVF cycles performed, pregnancy rate was lower in the study group (61.43% vs. 34.16%; p = 0.003), and this difference (p = 0.0151) remained in age-corrected rates, as well. The analyses were also performed in individual endocrinology groups. The prevalence of endocrine disorders is high in females participating in IVF programs, and they are often accompanying each other. Even after proper correction, the presence of the endocrine disorder negatively influences the pregnancy rate in IVF treatment.

Reproductive Sciences (Thousand Oaks, Calif.)