Evaluation of a fertility awareness-based shared decision-making tool part 2:  Patient experiences

Abstract:
Objective: To assess patient experiences using a Shared Decision-Making (SDM) Tool for fertility awareness-based methods (FABMs) of family planning.

Methods: The study employed a prospective crossover design to evaluate impact of the SDM tool compared to usual practice when discussing FABMs with patients. Patients completed preand post-office visit surveys and an online survey six months later. The primary outcomes evaluated the effect of the SDM tool on patient satisfaction and FABM continuity of use rates.

Results: There was no significant difference in likelihood of changing family planning methods immediately after the office visit; however, by six months a significantly larger proportion of patients had started or changed FABMs in the experimental group (52%, 34/66) compared to the control group (36%, 24/66) (p = 0.04). Significantly more patients who used the tool and changed their FABM after their visit reported increased satisfaction with their FABM compared to control (50% vs. 17%, p = 0.022).

Conclusions: Use of the SDM tool increased persistent use of and satisfaction with chosen FABMs at six months. INNOVATIONS: The novel SDM tool can enhance patients' understanding and facilitate the selection of a more suitable method leading to increased satisfaction.


The optimal time for laparoscopic excision of ovarian endometrioma: a prospective  randomized controlled trial

Lin Wu

First Affiliated Hospital of Xiamen University

Abstract:
Objective: This study aimed to explore the optimal time of laparoscopic cystectomy for unilateral ovarian endometrioma patients and evaluate the influence on ovarian reserve.

Materials and Methods: This prospective randomized controlled study included 88 women with unilateral ovarian endometrioma at a tertiary teaching hospital. All patients received their first identified diagnosis of ovarian endometrioma by ultrasound (> 4 cm and ≤ 10 cm) and were administered an oral contraceptive pill (OC) for one cycle before laparoscopy. They were randomly divided into two groups: laparoscopy at the late luteal phase (group LLP) (n = 44) (termination of OC for two days) and laparoscopy at the early follicular phase (group EFP) (n = 44) (day 3 after menstruation). Basic clinical characteristics were recorded. Serum Anti-Müllerian hormone (AMH) levels were measured at various times to predict ovarian reserve. Serum levels of Anti-Müllerian hormone (AMH) were measured at several time sites to predict the ovarian reserve; AMH and leukocyte esterase (LE) levels of the endometrioma wall were measured.

Results: Before surgery, serum AMH levels decreased in both groups from preoperative to one week and six months postoperatively. In contrast, the difference values of group EFP were larger than those of group LLP at postoperative one week and postoperative six months (1.87 ± 0.97 vs. 1.31 ± 0.93, P = 0.07; 1.91 ± 1.06 vs. 1.54 ± 0.93, P = 0.001). The mean rates of postoperative serum AMH decline were 37.92% and 46.34% in group EFP, significantly higher than those in group LLP (25.83% vs. 31.43%, P < 0.001). Ovarian endometrioma wall AMH of group LLP was significantly lower than that of group EFP ([22.86 ± 3.74] vs. [31.02 ± 5.23], P < 0.001). Meanwhile, ovarian endometrioma LE concentration of group LLP was significantly higher than that of group EFP ([482.83 ± 115.88] vs. [371.68 ± 84.49], P<0.001). There was also a significant inverse correlation between leukocyte esterase and AMH concentration in an ovarian endometrioma cyst wall (r=-0.564, P<0.001). CONCLUSION(S): The optimal time for laparoscopic cystectomy for patients with first identified unilateral ovarian endometrioma is the late luteal phase, which reduces ovarian tissue loss and preserves ovarian reserve effectively and safely.

Reproductive Biology and Endocrinology : RB&E


Recent trends in term trial of labor after cesarean by number of prior cesarean  deliveries

Cara Buskmiller

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

Beth L Pineles

Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX (Drs Pineles, Buskmiller, Qureshey,...

Abstract:
Background: Cesarean delivery is a major source of maternal morbidity, and repeat cesarean delivery accounts for 40% of cesarean delivery, but recent data on the trial of labor after cesarean and vaginal birth after cesarean are limited.

Objective: This study aimed to report the national rates of trial of labor after cesarean and vaginal birth after cesarean by number of previous cesarean deliveries and examine the effect of demographic and clinical characteristics on these rates.

Study Design: This was a population-based cohort study using the US natality data files. The study sample was restricted to 4,135,247 nonanomalous singleton, cephalic deliveries between 37 and 42 weeks of gestation, with a history of previous cesarean delivery and delivered in a hospital between 2010 and 2019. Deliveries were grouped by number of previous cesarean deliveries (1, 2, or ≥3). The trial of labor after cesarean (deliveries with labor among deliveries with previous cesarean delivery) and vaginal birth after cesarean (vaginal deliveries among trial of labor after cesarean) rates were computed for each year. The rates were further subgrouped by history of previous vaginal delivery. Year of delivery, number of previous cesarean deliveries, history of previous cesarean delivery, age, race and ethnicity, maternal education, obesity, diabetes mellitus, hypertension, inadequate prenatal care, Medicaid payer, and gestational age were examined concerning the trial of labor after cesarean and vaginal birth after cesarean using multiple logistic regression. SAS software (version 9.4) was used for all analyses.

Results: The trial of labor after cesarean rates increased from 14.4% in 2010 to 19.6% in 2019 (P<.001). This trend was seen in all categories of number of previous cesarean deliveries. Moreover, vaginal birth after cesarean rates increased from 68.5% in 2010 to 74.3% in 2019. The trial of labor after cesarean and vaginal birth after cesarean rates were the highest for deliveries with a history of both 1 previous cesarean delivery and a vaginal delivery (28.9% and 79.7%, respectively) and the lowest for those with a history of ≥3 previous cesarean deliveries and no history of vaginal delivery (4.5% and 46.9%, respectively). Factors associated with the trial of labor after cesarean and vaginal birth after cesarean rates are similar, but several factors have different directions of effect, such as non-White race and ethnicity, which is associated with a higher likelihood of trial of labor after cesarean but a lower likelihood of successful vaginal birth after cesarean.

Conclusion: More than 80% of patients with a history of previous cesarean delivery deliver by repeat scheduled cesarean delivery. With vaginal birth after cesarean rates increasing among those who attempt a trial of labor after cesarean, emphasis should be put on safely increasing the trial of labor after cesarean rates.


Contraceptives as abortifacients

Contraceptives as abortifacients

American Journal of Obstetrics and Gynecology


Detection and characterization of microplastics in the human testis and semen

Qiuhong Zhao

University of Tennessee Health Science Center

Yue Cao

Affiliated Hospital of Southwest Medical University

Zhiqiang Zhang

Tianjin Medical University General Hospital

Abstract: The health risk of microplastics (MPs) is a growing global concern. Evidence of reproductive health damage caused by the accumulation of MPs in males is still lacking. In the present study, 6 testis and 30 semen samples were collected, and MPs were detected using both pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and laser direct infrared spectroscopy (LD-IR). The results showed that MPs were detected in both testis and semen, with an average abundance of 0.23 ± 0.45 particles/mL in semen and 11.60 ± 15.52 particles/g in testis. Microplastics in the testis were composed of polystyrene (PS) with 67.7 %, while polyethylene (PE) and polyvinyl chloride (PVC) were the predominant polymers in semen. Compared to fragments, fiber, and film detected in semen, the fragment was the main shape the in testis. The sizes of these microplastics ranged from 21.76 μm to 286.71 μm, and most (67 % and 80.6 %) were 20-100 μm in semen and testis. In summary, this study revealed for the first time that MPs pollute the human male reproductive system and that various MP characteristics appear in different regions, which provides critical information and basic data for the risk assessment of MPs to human health.


Population-based cohort study of oral contraceptive use and risk of depression

Abstract:
Aim: Research on the effect of oral contraceptive (OC) use on the risk of depression shows inconsistent findings, especially in adult OC users. One possible reason for this inconsistency is the omission of women who discontinue OCs due to adverse mood effects, leading to healthy user bias. To address this issue, we aim to estimate the risk of depression that is associated with the initiation of OCs as well as the effect of OC use on lifetime risk of depression.

Methods: This is a population-based cohort study based on data from 264,557 women from the UK Biobank. Incidence of depression was addressed via interviews, inpatient hospital or primary care data. The hazard ratio (HR) between OC use and incident depression was estimated by multivariable Cox regression with OC use as a time-varying exposure. To validate causality, we examined familial confounding in 7,354 sibling pairs.

Results: We observed that the first 2 years of OC use were associated with a higher rate of depression compared to never users (HR = 1.71, 95% confidence interval [CI]: 1.55-1.88). Although the risk was not as pronounced beyond the first 2 years, ever OC use was still associated with an increased lifetime risk of depression (HR = 1.05, 95% CI: 1.01-1.09). Previous OC use were associated with a higher rate of depression compared to never users, with adolescent OC users driving the increased hazard (HR = 1.18, 95% CI: 1.12-1.25). No significant association were observed among adult OC users who had previously used OCs (HR = 1.00, 95% CI: 0.95-1.04). Notably, the sibling analysis provided further evidence for a causal effect of OC use on the risk of depression.

Conclusions: Our findings suggest that the use of OCs, particularly during the first 2 years, increases the risk of depression. Additionally, OC use during adolescence might increase the risk of depression later in life. Our results are consistent with a causal relationship between OC use and depression, as supported by the sibling analysis. This study highlights the importance of considering the healthy user bias as well as family-level confounding in studies of OC use and mental health outcomes. Physicians and patients should be aware of this potential risk when considering OCs, and individualized risk-benefit assessments should be conducted.


Intraovarian Platelet-Rich Plasma Injections: Safety and Thoughts on Efficacy  Based on a Single Centre Experience With 469 Women

Aliki Anifantaki

Centre for Technological Research of Crete

Mattheos Fraidakis

Foundation for Research and Technology Hellas

Abstract:
Background: Ovarian rejuvenation is an innovative procedure intended to restore ovarian fertility and development during the climacteric and has been used to enhance fertility in women with premature ovarian insufficiency (POI). This retrospective study was conducted to determine the effects of an intraovarian platelet-rich plasma (PRP) injection on ovarian stimulation outcomes in women referred to an in vitro fertilisation centre. Methods-

Population: This was a retrospective observational study, and the inclusion criteria included women of reproductive age with at least one ovary with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure. During the patient's first consultation, a detailed reproductive history was recorded, a pelvic scan for ovarian size was conducted, and hormonal analysis for follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), and luteinizing hormone (LH) was conducted.

Results: In the study, 469 women with a history of infertility, hormonal abnormalities, an absence of a menstrual cycle, and premature ovarian failure had hormonal levels recorded up to four months after treatment, and these were included in the study. The volume of peripheral blood required to prepare 6-8 mL of PRP for administration was 40-60 mL. The initial concentration of platelets in the peripheral blood sample was about 25000/µL, whereas the prepared PRP had a concentration of 900.000/µL. A volume of approximately 2-4 mL per ovary, depending on the ovarian volume, was used for the intraovarian injection. PRP intervention had significant effects on FSH concentration at the α = 0.05 level. Statistically significant increases in normal values of FSH and E2were observed for months three and four after the PRP intervention for all age groups.

Conclusions: The results of our observational study revealed that a PRP intraovarian injection is associated with improved ovarian tissue and function. Future randomised clinical trials are needed to shed light on the use of PRP in ovarian rejuvenation before offering it routinely in clinical practice.


Impact of Transfer of Maternal Care for Fetal Anomalies on Maternal Depression  and Anxiety Screening: A Prospective Cohort at a Tertiary Care Center

Lauren L Gray

Texas Children's Fetal Center, Baylor College of Medicine, Houston, Texas, USA.

Abstract:
Introduction: Perinatal depression and anxiety are major causes of maternal morbidity, and are more common in high-risk pregnancies compared to low-risk pregnancies. This study used validated screening tools to assess the prevalence of depression and anxiety symptoms in pregnant patients who transferred their obstetric care to a specialized fetal center for fetal anomaly.

Methods: This is a prospective cohort of patients with a fetal anomaly prompting transfer of obstetric care to Texas Children's Hospital Fetal Center between January 2021 and February 2022. The primary outcome was a self-assessed Edinburgh Postnatal Depression Scale score of 13 or higher, either antepartum or postpartum ("ever-positive EPDS"). Secondary outcomes included self-assessed Perinatal Anxiety Screening Scale (PASS) scores of 21 or higher ("ever-positive PASS"), obstetric outcomes, and neonatal outcomes. A frequentist analysis was performed.

Results: Of 149 women who transferred to Texas Children's Hospital during the study period, 94 enrolled in this study. Twenty-six percent of women had an ever-positive EPDS; 20% of patients had an ever-positive PASS. Patients were more likely to have an ever-positive EPDS if they were single (46% compared to 20%, p = 0.025). Women who had an ever-positive EPDS were more likely to be referred to psychiatry (46% compared to 14%, p = 0.004) and psychotherapy (29% compared to 1%, p < 0.001). Surprisingly, patients were more likely to have an ever-positive PASS if they reported good social support (p = 0.03). Antepartum EPDS and PASS scores had no relationship with postpartum EPDS scores.

Conclusion: Women who transfer care to a tertiary setting have positive EPDS scores at double the rate of the general population, but tend to experience this either antepartum or postpartum (not both). Fetal centers should be prepared to screen for mental health symptoms before and after delivery and provide appropriate referral or treatment.


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

Christine L Hitchcock

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1-2017/4. We randomized untreated, non-depressed, screenand baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35-58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0-4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2-4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference - 1.51). However, the 95% CI [- 3.97, 0.95] P = 0.222, did not exclude 3, a minimal clinically important difference. Women perceived progesterone caused decreased night sweats (P = 0.023) and improved sleep quality (P = 0.005); it decreased perimenopause-related life interference (P = 0.017) without increased depression. No serious adverse events occurred. Perimenopausal night sweats ± hot flushes are variable; this RCT was underpowered but could not exclude a minimal clinically important VMS benefit. Perceived night sweats and sleep quality significantly improved.


Defining embryo donation: an Ethics Committee opinion

Ethics Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org

Abstract: Building families through the adoption of children has been supported by human society throughout history. The ethical appropriateness of patients donating embryos to other patients for family building, or for research, is well established and is affirmed by this Committee. The use of the term ''adoption'' for embryos is inaccurate and should be avoided. This document replaces the ASRM Ethics Committee statement by the same name, last published in 2016.


Informed consent in assisted reproduction: an Ethics Committee opinion

Ethics Committee of the American Society for Reproductive Medicine

Abstract: Informed consent is a process in which the patient is supported in developing an understanding of medical options (including risks, benefits, and alternatives) and coming to a voluntary and autonomous decision.


Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series

Abstract:
Purpose: Low-dose naltrexone (LDN) has increased in popularity as a non-opioid medication that may decrease chronic pain symptoms. LDN is most commonly used to treat fibromyalgia, complex regional pain syndrome (CRPS), and painful diabetic neuropathy. Other studies suggest that LDN provides general symptom reduction in inflammatory conditions such as Crohn's disease and multiple sclerosis. We reviewed our experience with patients to whom we have prescribed LDN to see what types of painful conditions were most responsive to LDN in our patient population.Patients and methodsCharts from patients who came to the Pain Center between 2014 and 2021 were reviewed.

Results: Of the n = 137 patients who were prescribed LDN, 44% had no evidence of ever filling the prescription, and 4.4% of the responses were not charted. Of the remaining who took LDN (n = 70), 64% had some relief and were designated as 'Responders'. The most common pain diagnosis was neuropathic pain which, when added to the diagnosis of complex regional pain syndrome, accounted for 51% of responders to LDN. Patients who experienced greater than 50% pain relief from LDN were more likely to have the diagnosis of neuropathic pain or complex regional pain syndrome (p = 0.038, Fisher's Exact Test). There was a significant difference in the diagnosis of patients who responded to LDN. Patients with spondylosis were much less likely to respond to LDN when compared with other diagnoses (p = 0.00435, Chi-Square Test).

Conclusion: Patients with all types of neuropathic pain, including CRPS, were significantly more likely to have pain relief from LDN than patients with spondylosis (p=0.018). The diagnosis of spondylosis was more often associated with a lack of response to LDN than any other diagnosis. Patients may need to have a trial of several weeks before analgesic effects are seen with LDN.


Letrozole replaces clomiphene as first-line for PCOS ovulation induction

Abstract: Metabolic optimization + letrozole -> clomiphene -> OWR


A randomized trial of web-based fertility-tracking software and fecundability

Kenneth J Rothman

Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Abstract:
Objective: To assess the effect of randomization to FertilityFriend.com, a mobile computing fertility-tracking app, on fecundability.
Design: Parallel non-blinded randomized controlled trial nested within the Pregnancy Study Online (PRESTO), a North American preconception cohort. PATIENT(S): Female participants aged 21 to 45 years attempting conception for ≤6 menstrual cycles at enrolment (2013-2019).

Intervention: Randomization (1:1) of 5532 participants to receive a premium Fertility Friend (FF) subscription. MAIN OUTCOME MEASURE(S): Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only).

Results: Using life-table methods, 64% of the 2775 participants randomized to FF and 63% of the 2767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0-1 cycles of attempt time at enrolment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR = 0.97; 95% CI, 0.90-1.04) or within strata of pregnancy attempt time at enrolment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR = 1.06; 95% CI, 0.99-1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrolment (FR = 1.15; 95% CI, 0.98-1.35 for 3-4 cycles; FR = 1.14; 95% CI, 0.87-1.48 for 5-6 cycles), were aged <25 years (FR = 1.29; 95% CI, 1.01-1.66), had ≤12 years of education (FR = 1.32; 95% CI, 0.92-1.89), or were non-users of hormonal contraception within 3 months before enrolment (FR = 1.10; 95% CI, 1.02-1.19).

Conclusion: No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding.


Fertility Treatment 2021: Preliminary Trends and Figures

Human Fertilisation and Embryology Authority

Abstract:
# Fertility treatment 2021: preliminary trends and figures
Preliminary UK statistics for IVF and DI treatment, storage, and donation
Published: June 2023
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/5zzh25zw/fertility-treatment-2021-preliminary-trends-and-figures-underlying-dataset.xlsx "Fertility treatment 2021: preliminary trends and figures - underlying dataset")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#main-points)
- [Note on preliminary data](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#note-on-preliminary-data)
- [Section 1. Average IVF pregnancy rates using fresh embryo transfers increased for all ages](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-1)
- [Section 2. Average IVF pregnancy and birth rates using frozen embryo transfers increased over the past 30 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-2)
- [Section 3. Fertility treatments have returned to pre-pandemic levels](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-3)
- [Section 4. Multiple births from IVF at lowest UK average yet of 5%](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-4)
- [Section 5. Egg and embryo storage cycles continued to increase](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-and-figures/#section-5)
- [Section 6. Average age of IVF patients increased to 36 years](https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2021-preliminary-trends-a...


Dermal exposure to bisphenols in pregnant women's and baby clothes: Risk characterization

Abstract: Textile manufacturing consists of a multiple-step process in which a wide range of chemicals is used, some of them remaining in the final product. Bisphenols (BPs) are non-intentionally added compounds in textiles, whose prolonged skin contact may mean a significant source of daily human exposure, especially in vulnerable groups of the population. The present study aimed to determine the levels of bisphenol A (BPA) and some BP analogs (BPB, BPF, and BPS) in 120 new clothes commercialized in Spain for pregnant women, newborns, and toddlers. In addition, exposure assessment and risk characterization were also carried out. Traces of BPA were found in all the samples, with a median concentration of 7.43 ng/g. The highest values were detected in textile samples made of polyester. Regarding natural fibers, higher concentrations of BPs were observed in garments made of conventional cotton than in those made of organic cotton, with a significant difference for BPS (1.24 vs. 0.76 ng/g, p < 0.05). Although toddlers have a larger skin-area-to-body-weight ratio, pregnant women showed higher exposure to BPs than children. Anyhow, the non-carcinogenic risks associated with BPA exposure were below the unity, even under the upper-bound scenario. However, risks could be underestimated because other exposure routes were not considered in this study. The use of BPA has been restricted in some food-related products; therefore, BPA should also be regulated in the textile industry.


The effect of a video intervention on knowledge, awareness and perception of Natural Procreative Technology (NaProTechnology) among pharmacy undergraduate students in Nigeria

Abstract:
Background
Natural Procreative Technology (NaProTechnology) is a system of management of infertility and other reproductive health issues which requires the application of a woman’s observation and record of key events throughout her menstrual cycle.

Objectives
The study assessed the knowledge, awareness, and perception of NaProTechnology as well as the effect of an educational intervention among pharmacy undergraduate students at University of Nigeria, Nsukka.

Methods
It was a cross-sectional, questionnaire-based study. The ethical approval was obtained from the research ethics committee of the Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka. At baseline, the knowledge, awareness and perception of the students were assessed. Followed by the administration of an educational video on NaProTechnology. Then a post intervention survey was done to assess the effect of the educational intervention.

Key finding: s
There were 410 and 350 students in the preand post-intervention surveys respectively with relatively equal number of males and females. Majority were between 18 and 29 years old. Less than 5% were married while the highest proportion of the respondents were from 300 level The knowledge, awareness, and positive perception of NaProTechnology among the pharmacy students prior to intervention were poor but improved markedly post intervention (P < 0.001).
Conclusion
A video intervention was effective in improving the short-term knowledge, awareness and positive perception of NaProTechnology among pharmacy students.

Key message: s
What is already known on this topic?
Natural Procreative Technology (NaProTechnology) is a system of management of infertility based on the observation and record of fertility biomarkers by a woman.

What this study add: s?
The level of knowledge, awareness, and positive perception of NaProTechnology among the pharmacy undergraduates students were poor prior to a video intervention but improved markedly afterwards
How this study might affect research, practice or policy?
This study would lead to the public health system approach of informing, educating and communicating NaProTechnology to pharmacy students to achieve long-term effects by using well-designed courses and curriculum implementation.


Editorial: Immunocellular mechanisms and endocrine organs

Daniela Gallo

Azienda Socio Sanitaria Territoriale Lariana

Abstract: EDITORIAL article Front. Endocrinol., 16 May 2023Sec. Cellular Endocrinology Volume 14 - 2023 | https://doi.org/10.3389/fendo.2023.1214230


Application of systematic evidence mapping to identify available data on the potential human health hazards of selected market-relevant azo dyes

Abstract:
Background: Azo dyes are used in textiles and leather clothing. Human exposure can occur from wearing textiles containing azo dyes. Since the body's enzymes and microbiome can cleave azo dyes, potentially resulting in mutagenic or carcinogenic metabolites, there is also an indirect health concern on the parent compounds. While several hazardous azo dyes are banned, many more are still in use that have not been evaluated systematically for potential health concerns. This systematic evidence map (SEM) aims to compile and categorize the available toxicological evidence on the potential human health risks of a set of 30 market-relevant azo dyes.

Methods: Peer-reviewed and gray literature was searched and over 20,000 studies were identified. These were filtered using Sciome Workbench for Interactive computer-Facilitated Text-mining (SWIFT) Review software with evidence stream tags (human, animal, in vitro) yielding 12,800 unique records. SWIFT Active (a machine-learning software) further facilitated title/abstract screening. DistillerSR software was used for additional title/abstract, full-text screening, and data extraction.Results187 studies were identified that met populations, exposures, comparators, and outcomes (PECO) criteria. From this pool, 54 human, 78 animal, and 61 genotoxicity studies were extracted into a literature inventory. Toxicological evidence was abundant for three azo dyes (also used as food additives) and sparse for five of the remaining 27 compounds. Complementary search in ECHA's REACH database for summaries of unpublished study reports revealed evidence for all 30 dyes. The question arose of how this information can be fed into an SEM process. Proper identification of prioritized dyes from various databases (including U.S. EPA's CompTox Chemicals Dashboard) turned out to be a challenge. Evidence compiled by this SEM project can be evaluated for subsequent use in problem formulation efforts to inform potential regulatory needs and prepare for a more efficient and targeted evaluation in the future for human health assessments.


Bone health and prevalent fractures in women with polycystic ovary syndrome: a  meta-analysis and endocrine-context pathophysiology review

Sonia Shirin

University of British Columbia, Vancouver, BC, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Introduction: Bone health in those with Polycystic Ovary Syndrome (PCOS) is complex, but the general consensus is that cortical areal bone mineral density (aBMD) sites will be higher in PCOS than in ageand BMI-similar controls. However, spine aBMD sites may be lower, especially in non-obese PCOS. Whether or not incident fracture risk is increased in PCOS is currently controversial; no meta-analysis has yet assessed prevalent fractures. AREAS COVERED: We assessed the bone effects of PCOS-related ovarian hormone alterations, e.g. androgen excess, tonically normal/higher estradiol, and lower-than-normal progesterone levels. We also highlighted evidence that common PCOS medications (e.g. combined hormonal contraceptives [CHC], metformin, and spironolactone) have important bone effects. In adolescents, meta-analysis of CHC showed significant negative aBMD changes. Inflammation has negative PCOS bone effects and is linked with CHC use. EXPERT Opinion: Is fracture risk altered by PCOS? Our meta-analysis showed a 25% increased risk of prevalent fracture in PCOS versus controls; this did not reach statistical significance. Future prospective research needs to collect and evaluate ovulation characteristics, progesterone exposure, and adolescent CHC use, in addition to the complex variables that may influence risks for prevalent or incident fragility fractures and/or for cortical and cancellous aBMD values in PCOS.

Expert Review of Endocrinology & Metabolism


Menstrual cycle length variation by demographic characteristics from the Apple Women's Health Study

D D Baird

Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA

Shruthi Mahalingaiah

Department of Obstetrics & Gynecology, Boston University Medical Center, Boston, MA.

Abstract: Menstrual characteristics are important signs of women's health. Here we examine the variation of menstrual cycle length by age, ethnicity, and body weight using 165,668 cycles from 12,608 participants in the US using mobile menstrual tracking apps. After adjusting for all covariates, mean menstrual cycle length is shorter with older age across all age groups until age 50 and then became longer for those age 50 and older. Menstrual cycles are on average 1.6 (95%CI: 1.2, 2.0) days longer for Asian and 0.7 (95%CI: 0.4, 1.0) days longer for Hispanic participants compared to white non-Hispanic participants. Participants with BMI ≥ 40 kg/m2 have 1.5 (95%CI: 1.2, 1.8) days longer cycles compared to those with BMI between 18.5 and 25 kg/m2. Cycle variability is the lowest among participants aged 35-39 but are considerably higher by 46% (95%CI: 43%, 48%) and 45% (95%CI: 41%, 49%) among those aged under 20 and between 45-49. Cycle variability increase by 200% (95%CI: 191%, 210%) among those aged above 50 compared to those in the 35-39 age group. Compared to white participants, those who are Asian and Hispanic have larger cycle variability. Participants with obesity also have higher cycle variability. Here we confirm previous observations of changes in menstrual cycle pattern with age across reproductive life span and report new evidence on the differences of menstrual variation by ethnicity and obesity status. Future studies should explore the underlying determinants of the variation in menstrual characteristics.


Combined hormonal contraceptive use is not protective against musculoskeletal  conditions or injuries: a systematic review with data from 5 million females

Sarah Guy

City Sport + Physiotherapy Clinic, Vancouver, British Columbia, Canada.

Lynita White

Tall Tree Physiotherapy and Health Centre, Vancouver, British Columbia, Canada.

Abstract:
Objective: Assess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions.
Design: Systematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of Recommendations Assessment, Development and Evaluation approach.

Data Sources: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched from inception to April 2022. ELIGIBILITY: Intervention and cohort studies that assessed the association between new or ongoing use of CHC and an outcome of musculoskeletal tissue pathophysiology, injury or condition in postpubertal premenopausal females.

Results: Across 50 included studies, we assessed the effect of CHC use on 30 unique musculoskeletal outcomes (75% bone related). Serious risk of bias was judged present in 82% of studies, with 52% adequately adjusting for confounding. Meta-analyses were not possible due to poor outcome reporting, and heterogeneity in estimate statistics and comparison conditions. Based on semiquantitative synthesis, there is low certainty evidence that CHC use was associated with elevated future fracture risk (risk ratio 1.02-1.20) and total knee arthroplasty (risk ratio 1.00-1.36). There is very low certainty evidence of unclear relationships between CHC use and a wide range of bone turnover and bone health outcomes. Evidence about the effect of CHC use on musculoskeletal tissues beyond bone, and the influence of CHC use in adolescence versus adulthood, is limited.

Conclusion: Given a paucity of high certainty evidence that CHC use is protective against musculoskeletal pathophysiology, injury or conditions, it is premature and inappropriate to advocate, or prescribe CHC for these purposes. PROSPERO REGISTRATION NUMBER: This review was registered on PROSPERO CRD42021224582 on 8 January 2021.


GnRH agonists in the treatment of symptomatic endometriosis: a review

Eric S Surrey

Colorado Center for Reproductive Medicine

Abstract: The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents. Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative.


Evaluation of a fertility awareness-based shared decision-making tool part 1:  Study design and impact on clinician knowledge

Abstract:
Objective: To assess the impact of a Shared Decision-Making (SDM) tool for fertility awareness-based methods (FABMs) of family planning.

Methods: Clinicians familiar with at least one FABM were randomly invited to participate in a prospective cross-over study to compare usual practice to the use of the SDM tool when discussing FABMs with patients. Patients completed surveys preand post-office visit and six months later. The primary outcome explored the effect of online education on use of the SDM tool on clinicians' knowledge of FABMs.

Results: Of 278 clinicians contacted, 54% could not be reached, and 15% did not provide women's health services. The 26 clinicians enrolled were experienced, with more than half recommending FABMs for ≥10 years, and 73% recommending more than one FABM to patients. Knowledge scores significantly improved after online training and use of the SDM tool (baseline mean score = 9.54 (scale of 0-12); post-training mean score = 10.73, p < 0.002).

Conclusions: Education about FABMs and training on use of the SDM tool improved knowledge scores even among an experienced cohort of clinicians. INNOVATION: The novel SDM tool can better equip clinicians to meet the rising patient interest in FABMs.


Validation of a Brief Measure for Complicated Grief Specific to Reproductive  Loss

Cara Buskmiller

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

Jennifer Bute

Communication, Indiana University-Purdue University Indianapolis (IUPUI), Indianpolis, USA.

Michaelene Fredenburg

Institute of Reproductive Grief Care, San Diego, USA.

Abstract: Objective Complicated grief reactions follow some pregnancy outcomes, like miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. Stigma can delay treatment and worsen outcomes. Screening tools such as the Edinburgh Postnatal Depression Scale detect complicated grief poorly, and specific tools for prolonged or complicated grief after a reproductive loss are cumbersome. In this study, a five-item questionnaire to detect complicated grief after reproductive loss of any type was designed and preliminary validated. Methods A questionnaire patterned after the extensively validated Brief Grief Questionnaire (BGQ) was created by a group of physicians and lay advocates to employ non-traumatic but specific language related to grief after miscarriage, stillbirth, neonatal death, infant death, selective reduction, or termination of pregnancy. One hundred and forty women at a large academic center were recruited in person and via social media to validate the questionnaire with well-studied instruments for anxiety (7-item Panic Disorder Severity Scale, PDSS), trauma (22-item Impact of Events Scale), and reproductive grief and depressive symptoms (33-item Perinatal Grief Scale [PGS]). Results The response rate was 74.9%. Of the 140 participants, 18 (12.8%) experienced their loss during high-risk pregnancies, and 65 (46.4%) were recruited via social media. Seventy-one (51%) respondents had a score > 4, a positive screen for the BGQ. On average, women experienced their loss 2 years prior to participation (IQR 1-5 years). Cronbach's alpha was 0.77 (95% CI: 0.69-0.83). The goodness of fit indices of the model met Fornell and Larker criteria (RMSEA = 0.167, CFI = 0.89, SRMR = 0.06). The AVE was 0.42 and the CR 0.78. Conclusions This investigator-created screening tool is internally consistent and meets preliminary criteria for discriminant validity. This tool can be refined prior to testing for sensitivity and specificity in screening for complicated grief after a reproductive loss.


Efforts to transfer ectopic embryos to the uterine cavity: A systematic review

Miguel A Fernandez

Department of Obstetrics and Gynecology Georgetown University School of Medicine  Washington District of Columbia USA

Columba Thomas

Kennedy Institute of Ethics, Georgetown University, Washington, District of Columbia, USA.

Abstract:
Aim: The objectives of this review are to identify and characterize attempts to transfer ectopic embryos to the uterus, and to understand arguments for and against the feasibility of such an intervention.

Methods: An electronic literature search involved all English language articles published in MEDLINE (1948-), Web of Science (1899-), and Scopus (1960-) before July 1, 2022. Articles were included that identify or describe attempts to transfer the embryo from its ectopic location to the uterine cavity, or discuss the feasibility of such an intervention; there were no exclusion criteria (PROSPERO registration number CRD42022364913).

Results: The initial search yielded 3060 articles; 8 articles were included. Of these, two articles were case reports that described the successful transfer of the embryo from its ectopic location to the uterus, followed by term births; both cases involved laparotomy with salpingostomy, followed by transfer of the embryonic sac into the uterine cavity through an opening made in the uterine wall. The other six articles varied in type, and provided a number of arguments for and against the feasibility of such a procedure.

Conclusions: The evidence and arguments identified in this review may help manage expectations for those interested in transferring an ectopically implanted embryo in the hope of continuing the pregnancy, but who are uncertain about the extent to which such a procedure has been attempted or may be possible. Isolated case reports, with no evidence of replication, should be interpreted with the utmost caution and do not constitute a procedure for clinical use.

The Journal of Obstetrics and Gynaecology Research


The Influence of Gut Microbiota on Oxidative Stress and the Immune System

Abstract: The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of the entire organism. The gut microbiota generates a variety of metabolites and thereby regulates many biological processes, such as the regulation of the immune system. In the gut, bacteria are in direct contact with the host. The major challenge here is to prevent unwanted inflammatory reactions on one hand and on the other hand to ensure that the immune system can be activated when pathogens invade. Here the REDOX equilibrium is of utmost importance. This REDOX equilibrium is controlled by the microbiota either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for a stable REDOX balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced REDOX status directly affects the immune system by disrupting intracellular signaling and promoting inflammatory responses. Here we (i) focus on the most common reactive oxygen species (ROS) and (ii) define the transition from a balanced REDOX state to oxidative stress. Further, we (iii) describe the role of ROS in regulating the immune system and inflammatory responses. Thereafter, we (iv) examine the influence of microbiota on REDOX homeostasis and how shifts in proand anti-oxidative cellular conditions can suppress or promote immune responses or inflammation.


Physician Dispositions Toward Noninvasive Non-Hormonal Contraception

Abstract:
Introduction: Evidence-based, nonbiased, counseling on contraceptive options, followed by shared decision-making, is key in facilitating reproductive justice in a diverse population. An estimated 3% of contraceptive users in the United States use fertility awareness-based methods (FABMs) for contraception, and demand for these methods is increasing. FABMs can be a highly effective form of family planning when used in accordance with evidence-based protocols. They are preferred by some patients due to medical contraindications to hormonal contraceptives, lack of side effects, religious convictions, preference to avoid hormones or contraceptive devices, improved body literacy, or a combination of the above. FABMs are infrequently covered in medical school curricula and are often perceived by physicians to be of low efficacy. There is an opportunity for improvement of physicians' evidence-based knowledge of FABMs, which has the potential to improve patient understanding of and access to the full menu of family planning options.

Methods: A self-administered, cross-sectional survey was distributed to assess physician knowledge and opinions of FABMs by key university contacts. Univariate and bivariate statistics were calculated for close-ended questions and responses to open-ended questions were analyzed for common themes.

Results: A total of 79 participants completed the entire survey. Another 11 submitted partially completed surveys. For completed surveys, questions assessing knowledge of key concepts underlying FABMs, performance by specialty was 55% correct for OB/GYN (n = 16), 55% (n = 47) correct for family medicine, 36% (n = 10) correct for internal medicine, and 35% (n = 6) correct for pediatrics. Negative, neutral, mixed, and positive opinions related to FABMs were represented.

Conclusions: There are opportunities to improve physicians' evidence-based knowledge of FABMs; this may improve patient-centered contraceptive care.


Effectiveness of a Postpartum Breastfeeding Protocol for Avoiding Pregnancy

Abstract: The uses of cervical mucus and basal body temperature as indicators of return to fertility postpartum have resulted in high unintended pregnancy rates. In 2013, a study found that when women used urine hormone signs in a postpartum/breastfeeding protocol this resulted in fewer pregnancies. To improve the original protocol's effectiveness, three revisions were made: (1) women were to increase the number of days tested with the Clearblue Fertility Monitor, (2) an optional second luteinizing hormone test could be done in the evening, and (3) instructions were given to manage the beginning of the fertile window for the first six cycles postpartum. The purpose of this study was to determine the correct and typical use effectiveness rates to avoid pregnancy in women who used a revised postpartum/breastfeeding protocol. A cohort review of an established data set from 207 postpartum breastfeeding women who used the protocol to avoid pregnancy was completed using Kaplan-Meier survival analysis. Total pregnancy rates that included correct and incorrect use pregnancies were eighteen per one hundred women over twelve cycles of use. For the pregnancies that met a priori criteria, the correct use pregnancy rates were two per one hundred over twelve months and twelve cycles of use and typical use rates were four per one hundred women at twelve cycles of use. The protocol had fewer unplanned pregnancies than the original, however, the cost of the method increased.


The Risk of Infertility After Surgery for Benign Ovarian Cysts

Abstract: Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.


Plastic used in in vitro fertilization procedures induces massive placental gene expression alterations

Abstract: BACKGROUND: The exposure to plastic derivatives during human life is deleterious. Infants conceived using ART (IVF or ICSI) have twice as many risks of major birth defects compared to naturally conceived infants. Could plastic ware used during ART trigger defects in the fetal development? METHODS: Three groups of blastocysts were transferred to pseudopregnant mice. One was obtained after IVF and embryo development in plastic ware, the second in glass ware. The third, was obtained in vivo by natural mating. On day 16.5 of pregnancy, females were sacrificed and fetal organs collected for gene expression analysis. Fetal sex was determined by RT-PCR. RNA was extracted from a pool of five placental or brain samples coming from at least two litters from the same group and analyzed by hybridisation onto the mouse Affymetrix 430.2.0 GeneChips, confirmed by RT-qPCR for 22 genes. FINDINGS: This study highlights a major impact of plastic ware on placental gene expression (1121 significantly deregulated genes), while glassware was much closer to in vivo offspring (only 200 significantly deregulated genes). Gene Ontology indicated that the modified placental genes were mostly involved in stress, inflammation and detoxification. A sex specific analysis revealed in addition a more drastic effect on female than male placentas. In the brains, whatever the comparison, less than 50 genes were found deregulated. INTERPRETATION: Embryos incubated in plastic ware resulted in pregnancy with massive alterations of placental gene expression profile in concerted biological functions. There were no obvious effects on the brains. Besides other effects, this suggests that plastic ware in ART could be a cause of the increased level of pregnancy disorders observed recurrently in ART pregnancies. FUNDING: This study was funded by two grants from the Agence de la Biomedecine in 2017 and 2019.


Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial

Anni Rantala

Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, 90220 Oulu, Finland

Juha Tapanainen

Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290 Helsinki, Finland

Abstract: This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.


Age at Natural Menopause in Women Living with HIV: A Cross-Sectional Study Comparing Self-Reported and Biochemical Data

Shelly Tognazzini

Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.

Amber R Campbell

Women's Health Research Institute  Vancouver British Columbia Canada

Chelsea Elwood

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.


Microbiological and Cytokine Profiling of Menstrual Blood for the Assessment of Endometrial Receptivity: A Pilot Study

Abstract: Endometrial receptivity (ER) is a key factor required for the successful implantation of the embryo. However, the evaluation of ER is challenging, as a nondisruptive sampling of endometrial biomaterial by conventional methods is only possible outside of the embryo transfer (ET) cycle. We propose a novel approach for the assessment of ER-microbiological and cytokine profiling of menstrual blood aspirated directly from the uterine cavity at the beginning of the cryo-ET cycle. The aim of the pilot study was to evaluate its prognostic potential regarding the outcome of the in vitro fertilization procedure. Samples collected from a cohort of 42 patients undergoing cryo-ET were analyzed by a multiplex immunoassay (48 various cytokines, chemokines, and growth factors) and a real-time PCR assay (28 relevant microbial taxa and 3 members of the Herpesviridae family). Significant differences between groups of patients who achieved and did not achieve pregnancy were observed for G-CSF, GRO-α, IL-6, IL-9, MCP-1, M-CSF, SDF-1α, TNF-β, TRAIL, SCF, IP-10, and MIG (p < 0.05), whereas microbial profiles were not associated with the outcome of cryo-ET. It appeared that levels of IP-10 and SCGF-β were significantly lower (p < 0.05), in patients with endometriosis. Menstrual blood may provide great opportunities to noninvasively investigate various parameters of the endometrium.


Depression Associated With Hormonal Contraceptive Use as a Risk Indicator for  Postpartum Depression

Abstract:
Importance: Hormonal sensitivity may contribute to the risk of depression in some women, as observed during the premenstrual, postpartum, and perimenopausal phases, and when initiating hormonal contraception (HC). However, little evidence exists to support that such depressive episodes are linked across the reproductive life span.

Objective: To determine whether prior depression associated with HC initiation is coupled with a higher risk of postpartum depression (PPD) than prior depression not associated with HC initiation. DESIGN, SETTING, AND

Participants: This cohort study used Danish health registry data collected from January 1, 1995, through December 31, 2017, and analyzed from March 1, 2021, through January 1, 2023. All women living in Denmark born after 1978 with their first delivery between January 1, 1996, and June 30, 2017, were eligible for inclusion; 269 354 met these criteria. Women were then excluded if they had never used HC or if they had a depressive episode before 1996 or within 12 months prior to delivery.

Exposures: Prior depression associated with vs not associated with HC initiation, ie, if developed within 6 months after start of an HC exposure or not. Depression was defined as a hospital diagnosis of depression or filling a prescription for antidepressant medication.

MAIN OUTCOMES AND MEASURES: Crude and adjusted odds ratios (ORs) were calculated for the incidence of PPD defined as the development of depression within 6 months after first delivery.

Results: Of 188 648 first-time mothers, 5722 (3.0%) (mean [SD] age, 26.7 [3.9] years) had a history of depression associated with initiation of HC use, and 18 431 (9.8%) (mean [SD] age, 27.1 [3.8] years) had a history of depression not associated with the initiation of HC. Women with HC-associated depression had a higher risk of PPD than women with prior non-HC-associated depression (crude OR, 1.42 [95% CI, 1.24-1.64]; adjusted OR, 1.35 [95% CI, 1.17-1.56]).

Conclusions and Relevance: These findings suggest that a history of HC-associated depression may be associated with a higher risk of PPD, supporting that HC-associated depression may indicate PPD susceptibility. This finding offers a novel strategy in clinical PPD risk stratification and points to the existence of a hormone-sensitive subgroup of women.


Embryology, Week 1

Embryology, Week 1

Abstract: Human embryogenesis is a complicated process by which a fertilized egg develops into an embryo. During the first eight weeks of development, the conceptus shifts from a single-celled zygote into a multi-layered, multi-dimensional fetus with primitively functioning organs. The continued growth and increased intra-embryonic complexity during the first eight weeks of development are highly dependent upon cell signaling, proliferation, and differentiation. Due to the intricacies involved, the development of the human embryo is divided into developmental events by week. Week 1 is a major part of the germinal stage of development, a period of time that continues from fertilization through uterine implantation. Important events that occur during the first week of human embryonic development include gamete approximation, contact and fusion of gametes, fertilization, mitotic cleavage of the blastomere, morula formation, blastocyst formation, and implantation of the blastocyst.


The association between dietary patterns and risk of miscarriage: a systematic  review and meta-analysis

Rima Dhillon‐Smith

Birmingham Women’s and Children’s NHS Foundation Trust

Rima Dhillon-Smith

Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, United Kingdom.

Abstract:
Importance: The evidence on the association between diet and miscarriage risk is scant and conflicting.

Objective: To summarize the evidence on the association between periconceptual diet and miscarriage risk in healthy women of reproductive age.

Data Sources: Electronic databases were searched from inception to August 2022 without restriction of regions, publication types, or languages. STUDY SELECTION AND SYNTHESIS: Experimental or observational studies were considered for inclusion. The population was healthy women of reproductive age. Exposure was periconception diet. Study quality was assessed using the modified Newcastle-Ottawa Scale. Summary effect sizes (odds ratio [OR] with 95% confidence interval [CI]) were calculated for each food category. MAIN

Outcomes: Miscarriage rate (as defined by primary studies).

Results: We included 20 studies (11 cohort and 9 case-control), of which 6 presented data suitable for meta-analysis (2 cohort and 4 case-control, n = 13,183 women). Our primary analyses suggest a reduction in miscarriage odds with high intake of the following food groups: fruit (OR, 0.39; 95% CI, 0.33-0.46), vegetables (OR, 0.59; 95% CI, 0.46-0.76), fruit and vegetables (OR, 0.63; 95% CI, 0.50-0.81), seafood (OR, 0.81; 95% CI, 0.71-0.92), dairy products (OR, 0.63; 95% CI, 0.54-0.73), eggs (OR, 0.81; 95% CI, 0.72-0.90), and cereal (grains) (OR, 0.67; 95% CI, 0.52-0.87). The evidence was uncertain for meat, red meat, white meat, fat and oil, and sugar substitutes. We did not find evidence of an association between adherence to predefined dietary patterns and miscarriage risk. However, a whole diet containing healthy foods as perceived by the trialists, or with a high Dietary Antioxidant Index score (OR, 0.43; 95% CI, 0.20-0.91) may be associated with a reduction in miscarriage risk. In contrast, a diet rich in processed food was demonstrated to be associated with increased miscarriage risk (OR, 1.97; 95% CI, 1.36-3.34). CONCLUSION AND RELEVANCE: A diet abundant in fruit, vegetables, seafood, dairy, eggs, and grain may be associated with lower miscarriage odds. Further interventional studies are required to accurately assess the effectiveness of periconception dietary modifications on miscarriage risk. PROSPERO Registration: CRD42020218133.


Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms

Abstract: Endometriosis is an estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the uterus. Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.

International journal of molecular sciences


Low-dose naltrexone for treatment of burning mouth syndrome

Abstract:
Objective: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]).

Study design: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed.

Results: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects.

Conclusions: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology


Laser therapy versus expectant management for selective fetal growth restriction  in monochorionic twins: A systematic review

Cara Buskmiller

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

Roopali V Donepudi

Texas Children's Fetal Center, Baylor College of Medicine, Houston, Texas, USA.

Abstract: Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.


Clinical efficacy of a novel method of fertility-preserving adenomyomectomy in infertile women with diffuse adenomyosis

Kwon H

University of Illinois at Urbana-Champaign

Abstract: Beneficial and detrimental effect of surgical adenomyomectomy is still controversial in infertile women with severely diffuse adenomyosis. The primary objective of this study was to assess whether a novel method of fertility-preserving adenomyomectomy could improve pregnancy rates. The secondary objective was to evaluate whether it could improve dysmenorrhea and menorrhagia symptoms in infertile patients with severe adenomyosis. A prospective clinical trial was conducted between December 2007 and September 2016. Fifty women with infertility due to adenomyosis were enrolled in this study after clinical assessments by infertility experts. A novel method of fertility-preserving adenomyomectomy was performed on 45 of 50 patients. The procedure included T- or transverse H-incision of the uterine serosa followed by preparation of the serosal flap, excision of the adenomyotic tissue using argon laser under ultrasonographic monitoring, and a novel technique of suturing between the residual myometrium and serosal flap. All patients obtained dysmenorrhea relief 6 months postoperatively (NRS 7.28 vs 1.56, P<.001). The amount of menstrual blood decreased significantly (140.44 vs 66.33 mL, P<.05). Of the 33 patients who attempted pregnancy postoperatively, 18 (54.5%) conceived either by natural means, in vitro fertilization and embryo transfer (IVF-ET), or thawing embryo transfer. Miscarriage occurred in 8 patients, while 10 (30.3%) had viable pregnancies. This novel method of adenomyomectomy resulted in improved pregnancy rates, as well as relief of dysmenorrhea and menorrhagia. This operation is effective in preserving fertility potential in infertile women with diffuse adenomyosis.


Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells  Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

Abstract: A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim of this study was to evaluate the beneficial effects of fisetin, a naturally occurring polyphenol that is frequently present in a variety of fruits and vegetables. Uterine fragments were injected intraperitoneally to cause endometriosis, and fisetin was given orally every day. At 14 days of treatment, laparotomy was performed, and the endometrial implants and peritoneal fluids were collected for histological, biochemical, and molecular analyses. Rats subjected to endometriosis presented important macroscopic and microscopic changes, increased mast cell (MC) infiltration, and fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, and volumes, as well as histological alterations, neutrophil infiltration, cytokines release, the number of MCs together with the expression of chymase and tryptase, and diminished α smooth muscle actin (α-sma) and transforming growth factor beta (TGF β) expressions. In addition, fisetin was able to reduce markers of oxidative stress as well as nitrotyrosine and Poly ADP ribose expressions and increase apoptosis in endometrial lesions. In conclusion, fisetin could represent a new therapeutic strategy to control endometriosis perhaps by targeting the MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway and oxidative stress.

International Journal of Molecular Sciences


Definition and Criteria for Diagnosing Cesarean Scar Disorder

Klein Meuleman SJM, Murji A, van den Bosch T, Donnez O, Grimbizis G, Saridogan E, Chantraine F, Bourne T, Timmerman D, Huirne JAF, de Leeuw RA

Abstract:
Importance: Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms.

Objective: To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition.
Design, Setting, and

Participants: A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022.

MAIN OUTCOMES AND MEASURES: Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche.

Results: In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis.

Conclusions and Relevance: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.


A Pilot Qualitative Case Study of Women's Experiences with Fertility  Awareness-Based Methods

Mei R Fu

Rutgers, The State University of New Jersey

Abstract: This pilot qualitative case study was able to elicit rich data enabling a description of how women went through the journey of achieving pregnancy using fertility awareness-based methods. Findings underscore that women preferred using natural ways to detect ovulation and would recommend other women to do so, but with healthcare providers' guidance. The findings of this case study can serve as a starting point to provide a framework to understand women's experiences of enduring trial and error with multiple fertility awareness-based methods before discovering their effective method. Findings emphasize the importance for healthcare providers to guide women in using fertility awareness-based methods.


An Overview of Postoperative Intraabdominal Adhesions and Their Role on Female Infertility: A Narrative Review

Abstract: Postoperative intraabdominal adhesions can occur after more than 90% of gynecologic surgeries. They not only cause chronic pelvic pain and small bowel obstruction, but are also one of the main reasons for infertility. Adhesions are not only a burden for the affected patients, but are also a burden for the healthcare system, since the treatment of adhesion-associated complications costs a considerable amount of money. The gold standard for the diagnosis of adhesions is by laparoscopy, although other methods, such as transvaginal hydro-laparoscopy, are being discussed as better alternatives. Ideally, adhesions are avoided inherently, by operating carefully and by using microsurgical principles. If this is not possible, gel barriers have been shown to be successful in reducing postoperative adhesions.


The genetic basis of endometriosis and comorbidity with other pain and  inflammatory conditions

Rahmioglu N, Mortlock S, Ghiasi M, Møller PL, Stefansdottir L, Galarneau G, Turman C, Danning R, Law MH, Sapkota Y, Christofidou P, Skarp S, Giri A, Banasik K, Krassowski M, Lepamets M, Marciniak B, Nõukas M, Perro D, Sliz E, Sobalska-Kwapis M, Thorleifsson G, Topbas-Selcuki NF, Vitonis A, Westergaard D, Arnadottir R, Burgdorf KS, Campbell A, Cheuk CSK, Clementi C, Cook J, De Vivo I, DiVasta A, Dorien O, Donoghue JF, Edwards T, Fontanillas P, Fung JN, Geirsson RT, Girling JE, Harkki P, Harris HR, Healey M, Heikinheimo O, Holdsworth-Carson S, Hostettler IC, Houlden H, Houshdaran S, Irwin JC, Jarvelin MR, Kamatani Y, Kennedy SH, Kepka E, Kettunen J, Kubo M, Kulig B, Kurra V, Laivuori H, Laufer MR, Lindgren CM, MacGregor S, Mangino M, Martin NG, Matalliotaki C, Matalliotakis M, Murray AD, Ndungu A, Nezhat C, Olsen CM, Opoku-Anane J, Padmanabhan S, Paranjpe M, Peters M, Polak G, Porteous DJ, Rabban J, Rexrode KM, Romanowicz H, Saare M, Saavalainen L, Schork AJ, Sen S, Shafrir AL, Siewierska-Górska A, Słomka M, Smith BH, Smolarz B, Szaflik T, Szyłło K, Takahashi A, Terry KL, Tomassetti C, Treloar SA, Vanhie A, Vincent K, Vo KC, Werring DJ, Zeggini E, Zervou MI, Adachi S, Buring JE, Ridker PM, D'Hooghe T, Goulielmos GN, Hapangama DK, Hayward C, Horne AW, Low SK, Martikainen H, Chasman DI, Rogers PAW, Saunders PT, Sirota M, Spector T, Strapagiel D, Tung JY, Whiteman DC, Giudice LC, Velez-Edwards DR, Uimari O, Kraft P, Salumets A, Nyholt DR, Mägi R, Stefansson K, Becker CM, Yurttas-Beim P, Steinthorsdottir V, Nyegaard M, Missmer SA, Montgomery GW, Morris AP, Zondervan KT

Abstract: Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.


Fallopian tube recanalization for the management of infertility

Anne Roberts

University of California, San Diego, 9300 Campus Point Drive, La Jolla, CA, 92037, USA. acroberts@ucsd.edu.

Abstract: Infertility is a world-wide problem, defined as failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. There are multiple causes for infertility involving both male and female factors. Fallopian tube occlusion is a common reason for female infertility. The initial attempts to treat proximal obstruction involved the use of a whalebone bougie positioned in the uterine cornua to dilate the proximal tube by Smith as early as 1849. Fluoroscopic fallopian tube recanalization for the treatment of infertility was first described in 1985. Since that time, there have been over 100 papers describing various methods for recanalization of occluded fallopian tubes. Fallopian tube recanalization is a minimally invasive procedure which is performed on an outpatient basis. It should be a first line therapy for patients with proximal occlusion of fallopian tubes.


Pelvic Inflammatory Disease

Pelvic Inflammatory Disease

Abstract: Pelvic inflammatory disease (PID) is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and/or ovaries. It is typically an ascending infection, spreading from the lower genital tract. The majority of cases of PID are related to a sexually transmitted infection. The diagnosis of PID is primarily clinical and should be suspected in female patients with lower abdominal or pelvic pain and genital tract tenderness. During the patient’s evaluation, other etiologies of pain, including ectopic pregnancy, should be considered and ruled out. PID is treated with antibiotics to cover the primary pathogens, including Neisseria gonorrhoeae and Chlamydia trachomatis. Short-term complications include tubo-ovarian or pelvic abscess. Long-term complications include ectopic pregnancy, infertility, and chronic pelvic pain. Early diagnosis and treatment can potentially prevent complications.


Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes

Abstract:
BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels.

METHODS: Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated.

RESULTS: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001).

CONCLUSIONS: Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.

International journal of environmental research and public health


Reproductive surgery: revisiting its origins and role in the modern management of  fertility

Pietro Bortoletto

Boston IVF, Waltham, Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic a...

Abstract: For years, reproductive surgery was the mainstay of reproductive care. With the evolution and ultimate success of in vitro fertilization (IVF), reproductive surgery became an adjuvant therapy, indicated mainly for severe symptoms or to enhance success rates with assisted reproductive technologies. As success rates for IVF have plateaued, and emerging data rekindles the enormous benefits of surgically correcting reproductive pathologies, there is renewed interest among reproductive surgeons in reviving research and surgical expertise in this area. In addition, new instrumentation and surgical techniques to preserve fertility have gained traction and will solidify the need to have skilled reproductive endocrinology and infertility surgeons in our practice.


Association of hormonal and reproductive risk factors with breast cancer in  Indian women: A systematic review of case-control studies

Swagata Brahmachari

Department of General Surgery, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.

Abstract: The incidence of breast cancer in India has seen a rapid increase in recent years. Hormonal and reproductive risk factors for breast cancer have been affected by socioeconomic development. Studies on breast cancer risk factors in India are limited by the small sample size and specific geographical area. The current systematic review was carried out to assess the association of hormonal and reproductive risk factors with breast cancer in Indian women. A systematic review of MEDLINE, Embase, Scopus, and Cochrane database of systematic reviews were done. Relevant case-control studies published in peer-reviewed indexed journals were analyzed for hormonal risk factors such as age at menarche, menopause, and first childbirth; breastfeeding; abortion; and oral contraceptive pills use. Younger age (<13 years) at menarche was associated with high risk (odds ratio 1.23-3.72). Other hormonal risk factors with strong association were age at first childbirth and menopause, parity, and duration of breastfeeding. Abortion and the use of contraceptive pills did not have a clear association with breast cancer. Hormonal risk factors have a higher association in premenopausal disease and estrogen receptor-positive tumors. There is a strong association between hormonal and reproductive risk factors and breast cancer in Indian women. The protective effect of breastfeeding is related to the cumulative duration of breastfeeding.


Screening of regulated aromatic amines in clothing marketed in Brazil and Spain: Assessment of human health risks

Abstract: Azo dyes used in textile products contain aromatic amines (AAs), which may be released into the environment after skin bacteria cleavage the azo bond. In Europe, 22 carcinogenic AAs are regulated. Unfortunately, no information is available in many non-European countries, including Brazil. This study aimed to determine the concentrations of 20 regulated AAs in clothes marketed in Brazil and Spain. Generally, higher levels of regulated AAs were found in samples sold in Brazil than in Spain, which is linked to the lack of regulation. Sixteen AAs showed concentrations above 5 mg/kg in samples commercialized in Brazil, while 11 exceeded that threshold in Spain. Regulated AAs with levels above 5 mg/kg were more found in synthetic clothes of pink color. Concentrations in clothing were also used to evaluate the dermal exposure to AAs in 3 vulnerable population groups. The highest exposure corresponded to 2,4-diaminoanisole for toddlers in Brazil and 4,4-oxydianiline for newborns in Spain. Non-cancer risks associated with exposure to 4,4-benzidine by Brazilian toddlers was 14.5 (above the threshold). On the other hand, 3,3-dichlorobenzidine was associated with potential cancer risks for newborns and toddlers in Brazil. Given this topic's importance, we recommend conducting continuous studies to determine the co-occurrence of carcinogenic substances.


Sexual and reproductive health experiences and care of adult women with cystic fibrosis

Raksha Jain

The University of Texas Southwestern Medical Center

Alana Fields

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Emily M Godfrey

University of Washington, Box354982, 4311 11th Ave NE, Seattle WA 98105, United States.

Traci M Kazmerski

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Center for Innovative Research on Gender Health Equity (CONVERGE), University of Pittsburgh, PA...

Sigrid L Ladores

School of Nursing, The University of Alabama at Birmingham, 1720 S. 2nd Ave., NB485-A, Birmingham, AL 35294, United States.

Olivia M Stransky

Center for Innovative Research on Gender Health Equity (CONVERGE), University of Pittsburgh, PA; 230 McKee Place Pittsburgh, Pittsburgh, PA 15213, United States.

Sandra Sufian

University of Illinois-Chicago, 5001N. Wolcott Ave. #205 Chicago, IL 60640, United States.

Jennifer L Taylor-Cousar

National Jewish Health, Denver, CO; 1400 Jackson Street, Denver, CO J318, United States.

Abstract:
Background: As survival and health improve in people with cystic fibrosis (CF), more women with CF (wwCF) are considering their sexual and reproductive health (SRH). This study compared SRH experiences, behaviors, and care utilization of wwCF to the general population and defined CF-impacted considerations and care preferences.

Methods: We surveyed wwCF aged ≥25 years regarding SRH and compared results to the US National Survey of Family Growth (NSFG;n = 4357) and friend controls(n = 123). We used descriptive statistics and chi-squared/Fisher's exact testing and linear regression for comparisons.

Results: A total of 460 wwCF (mean age 36.1 years) completed the survey. WwCF were less likely to report current contraceptive use (43%vs76% NSFG, p<0.001;60% friends, p = 0.005). Nearly 25% of wwCF reported worsened CF symptoms during their menstrual cycles, 50% experienced urinary incontinence, and 80% vulvovaginal candidiasis. WwCF were significantly less likely to be parents (46%vs62% friends, p = 0.015) and to have experienced pregnancy (37%vs78% NSFG, p<0.001;58% friends, p = 0.002). More wwCF required medical assistance to conceive (29%vs12% NSFG, p<0.001 and 5% friends, p<0.001). Eighty-four percent of wwCF view their CF doctor as their main physician and 41% report no primary care provider (vs19% friends; p<0.001). WwCF report suboptimal rates of contraceptive and preconception counseling/care and are less likely to have received HPV vaccination (42%vs55%friends, p = 0.02). Despite desiring SRH conversations with their CF team, <50% report discussing SRH topics.

Conclusion: WwCF have significantly different SRH experiences than non-CF peers. They report suboptimal SRH care compared to their preferences highlighting an urgent need to encourage SRH counseling/care in the CF model.

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society


Combined and progestagen-only hormonal contraceptives and breast cancer risk: A UK nested case-control study and meta-analysis

Abstract:
BACKGROUND: Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations.

METHODS AND FINDINGS: Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk.

CONCLUSIONS: This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.