Stroke and myocardial infarction with contemporary hormonal contraception:  real-world, nationwide, prospective cohort study

Christian Torp-Pedersen

Department of Cardiology, Nordsjaellands Hospital, Hilleroed, Denmark.

Abstract:
Objective: To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction.
Design: Real-world, nationwide, prospective cohort study.
Setting: Denmark, by use of national registries.

Participants: All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy.

Main Outcome Measures: First time diagnosis of ischaemic stroke or myocardial infarction at discharge.

Results: Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and ≤3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction).

Conclusions: Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method.


Abstract: Welcome to the Journal of Restorative Reproductive Medicine, the official journal of the International Institute for Restorative Reproductive Medicine! JRRM is a peer-reviewed, open-access medical journal for clinicians, scientists, professionals, and patients. Our vision is that JRRM will disseminate and promote evidence-based information to support and restore human fertility and reproductive health. Restorative reproductive medicine can be defined as approaches to systematically identify and treat underlying health conditions contributing to reproductive dysfunction and suboptimal reproductive health.1,2 In the case of subfertility, the aim is to restore the ability to have a healthy live birth, starting with natural intercourse in the fertile window.3 Consistent with this, JRRM approaches subfertility and recurrent miscarriage as related chronic conditions with many possible underlying contributors, including medical conditions, lifestyle, and environmental factors. The same framework applies to other conditions affected by or affecting human reproductive health, which is intertwined with somatic health.4-6 JRRM is particularly interested in articles from clinical medicine, physiology, epidemiology, data science, social sciences, and public health. Relevant clinical domains include, but are not limited to gynecology, andrology, endocrinology, infertility, midwifery, primary care, fertility cycle tracking. Occasionally, basic science or animal studies might be considered for publication, if they directly relate to the vision of JRRM. Articles not considered relevant to this journal include those focusing on the humanities or medical ethics, or research that does not focus on a restorative approach to human fertility and reproductive health. JRRM builds on a long history of tracking ovulation and the fertile window with fertility biomarkers, originally with the aim of natural regulation of fertility.7-10 In the past few decades, clinicians and investigators have explored the power and potential of applying these tools to medical evaluation and treatment.11-13 JRRM seeks to highlight and accelerate the development of scientific evidence linking fertility biomarkers and health. There are a growing number of high-quality journals related to human reproduction. JRRM focuses uniquely on restorative approaches to investigation and treatment, which often get less attention. There is a wide variety of motivations for the interest and engagement of patients and professionals in restorative reproductive medicine: preferences for less invasive natural approaches, commitments to patient empowerment, seeking answers for what is wrong, concerns about access and quality, reducing costs, and ethical and religious commitments.14-16 We all can benefit from a diversity of perspectives in the service of patients.17 All motivations are welcome at JRRM, as we focus together on a restorative approach to fertility and reproductive health


Exploring the Immunological Aspects and Treatments of Recurrent Pregnancy Loss and Recurrent Implantation Failure

Abstract: Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 24 weeks of gestation. It affects 3-5% of women who are attempting to conceive. RPL can stem from a variety of causes and is frequently associated with psychological distress and a diminished quality of life. By contrast, recurrent implantation failure (RIF) refers to the inability to achieve a successful pregnancy after three or more high-quality embryo transfers or at least two instances of egg donation. RIF shares several causative factors with RPL. The immunological underpinnings of these conditions involve alterations in uterine NK cells, reductions in M2 macrophages and myeloid-derived suppressor cells, an increased Th1/Th2 ratio, a decreased Treg/Th17 ratio, the presence of shared ≥3 HLA alleles between partners, and autoimmune disorders. Various therapeutic approaches have been employed to address these immunological concerns, achieving varying degrees of success, although some therapies remain contentious within the medical community. This review intends to explore the immunological factors implicated in RPL and RIF and to analyze the immunological treatments employed for these conditions, which may include steroids, intravenous immunoglobulins, calcineurin inhibitors, anti-TNF antibodies, intralipid infusions, granulocyte colony-stimulating factor, and lymphocyte immunotherapy.

International journal of molecular sciences


Hypertensive Blood Pressure in Adolescent Females With Polycystic Ovary Syndrome

Abstract:
INTRODUCTION: Polycystic ovary syndrome is associated with hypertension in women, but few population studies have examined findings among adolescents. This retrospective study examines PCOS and hypertensive blood pressure in a large adolescent population receiving routine healthcare.

METHODS: Among females aged 13-17 years who had a well-child visit with systolic/diastolic blood pressure measured in a Northern California healthcare system (2013-2019), the outcome of hypertensive blood pressure (≥130/80 mmHg) was examined. Polycystic ovary syndrome was based on clinical diagnosis (ICD-9/10 256.4/E28.2) within 1 year of the visit. Overweight and obesity were defined by BMI 85th to <95th percentile and ≥95th percentile, respectively; 1.7% with underweight (<5th percentile) were excluded. Multivariable logistic regression was used to examine the association of polycystic ovary syndrome and hypertensive blood pressure, adjusting for age, race/ethnicity, BMI category, and estimated neighborhood deprivation index. Analyses were conducted in 2023-2024.

RESULTS: The cohort included 224,418 females (mean age 14.9±1.4 years; 34.3% non-Hispanic White, 30.1% Hispanic, 19.5% Asian/Pacific Islander, and 9.7% Black). Overall, 18.7% had overweight and 15.8% had obesity. The prevalence of hypertensive blood pressure was 7.2%, much higher for those with polycystic ovary syndrome (18.2%) versus no polycystic ovary syndrome (7.1%, p<0.001). In adjusted analyses, polycystic ovary syndrome was associated with 1.25-fold greater odds of hypertensive blood pressure (95% CI=1.10, 1.42). Similar findings were seen among the subset with obesity (OR=1.23 [95% CI=1.06, 1.42]).

CONCLUSIONS: Nearly 1 in 5 adolescents with polycystic ovary syndrome had hypertensive blood pressure. Polycystic ovary syndrome was associated with 25% increased adjusted odds of hypertensive blood pressure, emphasizing the importance of blood pressure surveillance in this population with higher cardiometabolic risk.


Electronic health records-integrated mobile health interventions in primary care to improve hypertension management in Black/African American populations: a systematic review

Abstract: Black/African American individuals face twice the risk of hypertension compared to non-Hispanic Whites in the United States (US). A synergistic strategy integrating primary care with Electronic Health Records (EHR) and mobile health (mHealth) technologies may help address hypertension disparities. This unique strategy prioritizes early disease identification, improved care access, and self-management. However, limited research exists on how primary care can effectively integrate these components to reduce hypertension in Black/African American individuals. We aimed to (i) identify characteristics of Black/African American populations represented in EHR-driven mHealth interventions for hypertension management in primary care settings and (ii) identify the specific EHR-driven mHealth interventions. We used the PubMed, Web of Science, and Scopus databases to identify studies conducted in the US. The included articles focused on (i) Black/African American individuals, (ii) EHR and mHealth integration; (iii) primary care setting, and (iv) hypertension or blood pressure as the outcome. We screened 749 studies and synthesized 14. Combined, Black/African American patients were female (61%), 52.6 years on average, with diabetes health comorbidity (35%). Included studies utilized health monitoring devices (n = 14), smartphone applications (n = 11), interactive messaging (n = 8), and patient portals (n = 3). These tools facilitated health monitoring (n = 14), social networking (n = 3), and lifestyle counseling (n = 14). EHR-mHealth technologies in primary care show promise to improve hypertension management in Black/African American populations. Current interventions focus on enhancing health education access, continuous health monitoring, patient–physician communication, and social engagement. Further research is needed to optimize integration into clinical workflow for hypertension management.


Is endometriosis typology a potentially better classification system for  assessing risk of female infertility?

Leslie V Farland

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

Rachael B. Hemmert

Division of Public Health, Department of Family and Preventive Medicine, University of Utah Health, Salt Lake, UT, USA.

Abstract:
Objective: To determine whether endometriosis typology, namely ovarian endometriomas (OE), deep infiltrating endometriosis (DIE), or superficial endometriosis (SE), correlates with fertility history.
Design: Prospective cohort.
Setting: One of fourteen surgical centers in Salt Lake City, Utah (n = 5) or San Francisco, California (n = 9).

Patients: A total of 473 women (18-44 years) with no prior endometriosis diagnosis, undergoing laparoscopies/laparotomies, irrespective of indication, in Utah or California (2007-2009).

Exposure: Incident endometriosis.

Main Outcome Measures: Before surgery, we queried women about time to become pregnant for prior planned pregnancies. Generalized linear models were used to calculate adjusted prevalence ratios (aPR) for association between endometriosis typology and infertility, defined as having ever tried >12 months (>6 months for women ≥35 years) to get pregnant. We also generated fecundability odds ratios (aFOR) to capture time to pregnancy.

Results: Twenty-five percent (n = 116) of women were diagnosed with SE only, 5% (n = 23) with OE, 6% (n = 29) with DIE, and 5% (n = 22) with OE + DIE, and 60% (n = 283) with no endometriosis. Compared with women with no endometriosis, women with SE had a 1.58 higher aPR (95% confidence interval [CI], 1.16-2.14), although women with OE and/or DIE had a 2.41 higher aPR for subfertility after adjusting for women's age, body mass index, and site. Compared with women with no endometriosis, women with OE and/or DIE had a 53% lower historic fecundability (aFOR, 0.47; 95% CI, 0.24-0.95); however, no association was found among women with SE (aFOR, 0.81; 95% CI, 0.49-1.33).

Conclusions: Specific endometriosis typologies may be associated with fecundability, with OE and/or DIE associated with nearly a 150% higher prevalence of subfertility and over a 50% lower historic fecundability.


Condoms, IUDs, counseling and natural family planning

Jayshree J. Upadhye

Datta Meghe Institute of Medical Sciences

Aditi J. Upadhye

Department of Obstetrics and Gynecology, Upadhye Children Hospital, Nagpur, Maharashtra, India


O-195 Vipoglanstat, an oral non-hormonal treatment in clinical development for endometriosis

Abstract: Prostaglandin E2 (PGE2) is a key driver of endometriosis pathogenesis. Vipoglanstat selectively inhibits mPGES-1 enzyme activity. A Phase I trial involved 72 healthy volunteers receiving single or repeated doses, while Phase II included 69 subjects with chronic inflammatory disease receiving daily treatment. Results demonstrated the compound was safe and well tolerated at therapeutic doses and achieved complete mPGES-1 inhibition while preserving protective prostacyclin production. A Phase II endometriosis trial is scheduled to begin in 2025, focusing on pain reduction and lesion assessment via imaging.


Therapeutic Alternatives for the Hirsute Patient

Marya Ahsan

Imam Mohammad ibn Saud Islamic University

Ayaz Khurram Mallick

Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.


Clomiphene Citrate – Initiated Ovulation: The State of the Art


The Thermogenic Property of Progesterone

Qin Li

Ministry of Education of the People's Republic of China


The Effectiveness of the Ovulation Method as a Means of Achieving and Avoiding Pregnancy

Noemi Hamala

Department of Reproductive Medicine and Gynecological Endocrinology, University Hospital of Schleswig-Holstein, Campus Luebeck, and Universitaeres Kinderwunschzentrum Luebeck , Luebeck,

Sören von Otte

Department of Reproductive Medicine and Gynecological Endocrinology, University Hospital of Schleswig-Holstein, Campus Kiel, and Universitaeres Kinderwunschzentrum Kiel, Kiel, Germany.

Thomas W Hilgers

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


Hormonal Profiles in Users of the Ovulation Method

Manuela Farris

Saint Camillus International University of Health and Medical Sciences


Dietary supplements and prevention of preeclampsia

Abstract: Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE.

Hypertension research : official journal of the Japanese Society of Hypertension


Chronic Prurigo Associated With Allergic Contact Dermatitis: A Case Series Highlighting Textile Dyes and Fragrance Allergens

Abstract: ABSTRACTBackgroundChronic prurigo (CP) is a condition characterised by chronic pruritus and pruriginous lesions. While frequently associated with atopic dermatitis (AD), its link with allergic contact dermatitis (ACD) is less understood.ObjectivesTo describe the clinical features, diagnostic findings, and therapeutic outcomes of CP associated with ACD.Patients/Materials/MethodsThis case series included patients diagnosed with CP or prurigo nodularis, identified through medical records from a specialised ACD clinic. Inclusion criteria were positive patch tests identifying relevant allergens, complete medical histories, and resolution or improvement of CP lesions after allergen avoidance. Patch testing was performed using the Spanish Extended Baseline Series and additional allergen panels as needed, following International Contact Dermatitis Research Group guidelines.ResultsSix patients were identified: four cases of CP associated with fragrances and two with textile dyes. All patients improved significantly with allergen avoidance; two required dupilumab. Histological findings and clinical responses suggested a Th2‐driven immune response in fragrance‐induced ACD and a Th2/Th17 involvement in azo dye‐related cases.ConclusionsACD caused by textile dyes and fragrances may manifest as papular dermatitis with features consistent with CP. Patch testing should be considered for idiopathic CP or cases associated with AD. Further studies are needed to clarify the immune mechanisms underlying this association.


Plasma progesterone levels in normal and abnormal early human pregnancy


Network meta-analysis on the efficacy of different interventions for treating thin endometrium

Lin Wu

First Affiliated Hospital of Xiamen University

Zhiqiang Zhang

Tianjin Medical University General Hospital

Dongyan Li

Second Hospital of Shanxi Medical University


International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report for cycles conducted in 2017-2018

Abstract:
STUDY QUESTION: What were the rates of utilization, effectiveness, and safety for assisted reproductive technology (ART) throughout the world in 2017 and 2018, and what trends were observed?

SUMMARY ANSWER: The total reported number of ART fresh and frozen cycles conducted in 83 participating countries was 2 913 498 in 2017 and 3 303 505 in 2018, with 5-year trends including an increasing proportion of cycles utilizing frozen embryo transfer (FET) and an increasing number of cycles utilizing pre-implantation genetic testing (PGT).

WHAT IS KNOWN ALREADY: Prior reports from the International Committee Monitoring ART (ICMART) have reported on the utilization, effectiveness, and safety of ART from participating countries, with an increase in the number of cycles and number of participating countries over time. These reports have described regional differences in the utilization of ART overall, as well as differences in the utilization of specific practices such as ICSI, PGT and single embryo transfer. Past reports demonstrated that rates of delivery per cycle have increased and rates of multiple gestations have decreased over time.

STUDY DESIGN, SIZE, DURATION: This retrospective, cross-sectional survey describes ART procedures performed globally in 2017 and 2018. Data were submitted to ICMART by participating countries from national or regional registries.

PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 83 countries which provided data for cycles performed in 2017 or 2018, with the majority of countries providing data for both years. Aggregate data are reported for each participating country and analysed using methods developed by ICMART to calculate measures of utilization, effectiveness, and safety.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 2 913 498 cycles and 671 012 babies born were reported for treatment performed in 2017, increasing to 3 303 505 cycles and 728 383 babies born for treatment performed in 2018. After imputing data for non-reporting centres in reporting countries, the estimated number of cycles performed in 2017 was 3 107 188 resulting in an estimated 814 588 babies. For 2018, the estimated number of cycles was 3 568 635 resulting in an estimated 870 814 babies. Utilization of ICSI for autologous fresh non-PGT cycles declined slightly compared with 2014 (54.6% in 2017 and 57.3% in 2018 compared with 64.8% in 2014). The percentage of transfers which were of frozen embryos was 55.7 % in 2017 and 57.9% in 2018, up from 38.9% in 2014. Among all countries, including those which reported no 'freeze all' cycles, the percentage of 'freeze all' cycles was 30.5% in 2017 and 32.7% in 2018, up from 13.1% in 2014. In countries reporting at least one retrieval cycle in which all embryos were frozen, the percentage of retrievals with no fresh embryo transfer increased (36.2% in 2017 and 36.8% in 2018, up from 20.1% in 2014). The number of PGT cycles in 2018 (172 247) was nearly 5-fold higher than the number reported in 2014 (36 512) with wide regional variation in utilization of PGT observed. In 2017, the delivery rate for autologous oocytes was 23.5% per oocyte retrieval, with a cumulative delivery rate of 36.4% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.8% per autologous fresh transfer, 32.5% per autologous frozen transfer, and 47.3% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 33.1% (combined fresh transfer and frozen transfers). In 2018, the delivery rate for autologous oocytes was 23.8% per oocyte retrieval, with a cumulative delivery rate of 37.3% per retrieval (excluding cycles which utilized PGT). The delivery rates per embryo transfer were 31.3% per autologous fresh transfer, 31.9% per autologous frozen transfer, and 48.4% per transfer after PGT. The delivery rate for transfers utilizing donor oocytes was 34.3%. The multiple delivery rate with autologous fresh transfer was 19.7% in 2017, and 18.3% in 2018. For autologous FET, the multiple delivery rate was 16.2% in 2017, and 14.9% in 2018. With oocyte donation (combined fresh and frozen embryo transfers), the multiple delivery rate was 15.9% in 2017, and 13.4% in 2018. Finally, the multiple delivery rate for cycles utilizing PGT was 6.9% in 2017 and 5.5% in 2018.

LIMITATIONS, REASONS FOR CAUTION: The data and analysis presented are dependent on the quality and completeness of the data submitted to ICMART, which varies globally. There is little data from the Middle East and some countries in Asia. It is important to note that delivery rates per transfer after PGT required the availability of embryos suitable for transfer, and therefore should not be interpreted as suggesting that PGT increases the overall success of ART per oocyte retrieval. Because of an updated methodology in the calculation of delivery rates and number of babies born, direct comparisons with past reports for these metrics cannot be made. Data are observational and it


The Historic Review of the Clinical Use of Progesterone and Progestin


Fertility Treatment 2017: Trends and Figures

Human Fertilisation and Embryology Authority


Systematic review and meta-analysis of polycystic ovary syndrome and mental health among Black Asian Minority Ethnic populations

Abstract: Background: Polycystic ovary syndrome (PCOS) is a common, chronic gynaecological condition impacting women of reproductive age. Women with PCOS have hormonal, ovulatory, and metabolic dysfunction resulting in multiple symptoms. The correlation between hormonal disbalance and mental health outcomes in PCOS across Black Asian Minority Ethnic populations was investigated in this systematic review and meta-analysis. The review included 30 studies and data from nearly 4,000 women with PCOS. Major depressive disorder affected 17% of patients with PCOS, with a range from 0% to 67%. Black, Asian, and other underserved populations were found to have higher prevalence of mental health disorders exacerbated by PCOS.


Hormonal Contraception and Endometrial Thickness in IVF/ICSI Cycles: A Multicentre Historical Cohort Study

Abstract: OBJECTIVE: To study the association between previous use of levonorgestrel intrauterine system (LNG-IUS) and endometrial thickness (EMT) in women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Multicentre historical cohort study. SETTING: Eight Danish public and private fertility clinics. POPULATION: 12786 women aged 18-46 years contributing with an EMT measurement from 22 464 different IVF/ICSI treatment cycles between 2000 and 2021. METHODS: Exposure was previous use of LNG-IUS, combined oral contraceptive pills (OCPs), progestogen-only pills (POPs), no/other contraception or combined, cumulated use of contraception when more contraceptives had been used during the inclusion period. LNG-IUS use was categorised into 0-3 years, >3-6 years, >6-9 years and >9 years. Mixed effect logistic regression adjusted for age, BMI, smoking, educational level, total FSH dose and fertility clinic was used. MAIN OUTCOME MEASURE: EMT (< 7 mm vs >= 7 mm). RESULTS: Statistically significantly higher odds of EMT >= 7 mm were found for OCPs [OR 3.53 (95% CI 1.29-9.65)], POPs [OR 6.43 (95% CI 1.45-28.63)] and no/other contraception [OR 6.67 (95% CI 2.37-18.74)] relative to LNG-IUS in IVF/ICSI cycles. All duration categories of ever use of LNG-IUS were associated with significantly lower odds of EMT >= 7 mm compared to no/other contraception. CONCLUSIONS: Previous use of LNG-IUS was associated with decreased endometrial growth in women undergoing IVF/ICSI.

BJOG: An International Journal of Obstetrics and Gynaecology


Effectiveness and Safety of IVF Add-Ons: A Meta-Review of 10 Common IVF Add-Ons


'I don't know what normal has been': a grounded theory exploration of the journey to endometriosis diagnosis

Babu Karavadra

University of East Anglia, Norwich Medical School Norwich Research Park, Norwich, Norwich, NR4 7TJ, UK. B.Karavadra@nhs.net.


Investigating male factors and their relationships with reproductive health outcomes: a case-control study protocol for Towards Optimal Fertility, Fathering, and Fatherhood studY (TOFFFY) in Singapore

Abstract: INTRODUCTION: Despite the global prevalence of low fertility rates, male contributions to fertility and reproductive health outcomes have been understudied. This study aims to investigate the male contribution to fertility and explore the underlying biological mechanisms. Specifically, we aim to (1) identify male factors associated with successful pregnancy, (2) develop a fertility index incorporating modifiable factors for both males and females to predict pregnancy rate and (3) explore the relationship of male modifiable factors with semen parameters and molecular characteristics. METHODS AND ANALYSIS: We will conduct an unmatched case-control study involving 240 couples with impaired male fertility (cases) and 240 couples with normal male fertility (controls). Between July 2024 and June 2026, we will recruit 480 eligible couples from KK Women's and Children's Hospital, Singapore. Male and female participants will complete questionnaires on sociodemographics, general health and lifestyle factors, and their anthropometry and body fat composition will be measured. Blood and semen samples from the male participants will be collected for biochemical, molecular and semen analyses. Predictive male factors will be identified using the least absolute shrinkage and selection operator method, accounting for female factors. We will construct a logistic regression model incorporating both male and female factors to derive a fertility index, which will be evaluated using cross-validation on subsets of the study population. Multivariable linear regression will be used to explore relationships between male modifiable exposures and semen parameters. ETHICS AND DISSEMINATION: The study protocol has received approval from the Centralised Institutional Review Board of SingHealth (2024/2120), Singapore. Participants will provide written informed consent. Study results will be disseminated through conferences and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT06293235.


Expanding our Human Sexual Horizons

Expanding our Human Sexual Horizons

Thomas W Hilgers

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


PFC/PFAS concentrations in human milk and infant exposure through lactation: a comprehensive review

Abstract:
Abstract
          Per- and polyfluoroalkyl substances (PFAS), previously known as perfluorinated compounds (PFC), are a group of synthetic chemicals widely used over the past decades. Their extensive application, combined with their environmental persistence, has contributed to their ubiquitous presence in the environment and the associated toxicological risks. Regarding humans, blood serum testing remains the primary method for biomonitoring PFAS exposure, while breast milk has also been used due to the transfer of these substances from mothers to infants during lactation. This paper aims to review the scientific literature (using PubMed and Scopus databases) on PFAS concentrations in the breast milk of non-occupationally exposed women. Where available, the estimated daily intake of these compounds by breastfeeding infants is also examined. The reviewed studies are categorized by continent and country/region, revealing a significant lack of data for many countries, including both developed and developing nations. The findings indicate substantial variability in PFAS concentrations, influenced by factors such as geographic location, sampling year, and the specific PFAS analyzed. Among the identified compounds, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are most commonly detected, along with perfluorohexanesulfonic acid (PFHxS) and perfluorononanoic acid (PFNA), being the only PFAS with regulated maximum levels in certain foodstuffs. Most studies were conducted before the implementation of the current (updated) tolerable weekly intake (TWI) values for these substances. Consequently, the majority reported a low health risk for breastfeeding infants, even in high-intake scenarios. Nevertheless, biomonitoring studies are urgently needed in countries with limited or no data, and new investigations should assess whether current estimated intakes exceed the updated TWI. Special focus should be given to rural and industrial areas where exposure levels remain poorly understood.


Comparative analysis of human and mouse ovaries across age

Abstract: The mouse is a tractable model for human ovarian biology; however, its utility is limited by incomplete understanding of how transcription and signaling differ interspecifically and with age. We compared ovaries between species using three-dimensional imaging, single-cell transcriptomics, and functional studies. In mice, we mapped declining follicle numbers and oocyte competence during aging; in human ovaries, we identified cortical follicle pockets and decreases in density. Oocytes had species-specific gene expression patterns during growth that converged toward maturity. Age-related transcriptional changes were greater in oocytes than in granulosa cells across species, although mature oocytes change more in humans. We identified ovarian sympathetic nerves and glia; axon density increased in aged ovaries and, when ablated in mice, perturbed folliculogenesis. This comparative atlas defines shared and species-specific hallmarks of ovarian biology.


Hormonal imbalance in umbilical vein cord blood of pregnant women with endometriosis: a propensity score-matched analysis

Maìra Casalechi

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico


Pulmonary Endometriosis: A Clinical Review

Min Shi

Department of Pathology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China

Ting Zhou

Department of Radiology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China


DIR Jahrbuch 2024 (Deutsches IVF-Register Annual Report 2024)

Abstract: DIR Jahrbuch 2024 des Deutschen IVF-Registers. ENGLISH SUMMARY: 2024 Annual Report of the German IVF Registry (Deutsches IVF-Register, DIR). Reports German ART cycle counts, treatment indications, embryo-transfer outcomes, pregnancy and live-birth rates by treatment type, age strata, and cycle counts. The DIR is the largest German ART registry covering nearly all licensed reproductive medicine centers under voluntary professional-society registration.


Physicians need more education about natural family planning


National Summary Report 2023

National Summary Report 2023

Society for Assisted Reproductive Technology


Trends in Egg and Sperm Donation 2016

Trends in Egg and Sperm Donation 2016

Shelun Tsai

Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York; Pacific Northwest Fertility and IVF Specialists, Bellevue, Washington. Elec...


RRM outcomes compared to IVF: retrospective evaluation of a 2019 clinic cohort

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Craig Turczynski

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

Journal of Restorative Reproductive Medicine


Association of in vitro fertilization with severe maternal morbidity in low-risk patients without comorbidities

Abstract: OBJECTIVE: To determine whether an association exists between in vitro fertilization (IVF) and severe maternal morbidity among low-risk pregnant patients. DESIGN: Retrospective cohort study. SUBJECTS: Low-risk pregnant patients who delivered between January 2019 and December 2022. Low-risk was defined as having an obstetric comorbidity index score of 0. EXPOSURE: In vitro fertilization. MAIN OUTCOME MEASURE(S): The primary outcome (dependent variable) was any severe maternal morbidity. The secondary outcome was the need for a cesarean delivery. A modified Poisson regression with robust error variance was used to model the probability of severe maternal morbidity as a function of IVF. Risk ratios and their associated 95% confidence intervals (CIs) were computed. An α value of 0.05 was considered statistically significant. RESULT(S): A total of 39,668 pregnancies were included for analysis, and 454 (1.1%) were conceived by IVF. The overall severe maternal morbidity rate was 2.4% (n = 949), with the most common indicator being blood transfusion. The overall cesarean delivery rate was 18.8% (n = 7,459). On modified Poisson regression, IVF-conceived pregnancies were associated with 2.56 times the risk of severe maternal morbidity (95% CI, 1.73-3.79) and 1.54 times the risk of having a cesarean delivery (95% CI, 1.37-1.74) compared with non-IVF pregnancies. CONCLUSION(S): In vitro fertilization is associated with higher rates of severe maternal morbidity, primarily the need for a blood transfusion, and cesarean delivery in low-risk pregnancies without major comorbidities. Recognizing this association allows healthcare providers to implement proactive measures for better monitoring and tailored postpartum care.


Non-Invasive Matrices for the Human Biomonitoring of PFAS: An Updated Review of the Scientific Literature

Abstract: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in consumer and industrial products due to their unique physicochemical properties. However, their persistence and bioaccumulative potential pose significant environmental and human health risks. This review focuses on the use of non-invasive matrices—urine, hair, and nails—for the human biomonitoring of PFAS, highlighting key findings from scientific studies. While urine offers a non-invasive and practical option, its limited sensitivity for long-chain PFAS requires further analytical advances. Hair and nails have demonstrated potential for use in biomonitoring, with higher detection frequencies and concentrations for certain PFAS compared to urine. The variability in PFAS levels across studies reflects differences in population characteristics, exposure sources, and geographic regions. This review emphasizes the need for standardized analytical methods, expanded population studies, and the use of complementary matrices to enhance the accuracy and reliability of PFAS exposure assessment.


Ultrasonic Visualization of Human Ovulation

Hao Lin

Fuzhou Maternity and Child Health Care Hospital


Per- and Polyfluoroalkyl Substances (PFAS) in Consumer Products: An Overview of the Occurrence, Migration, and Exposure Assessment

Abstract: Per- and polyfluoroalkyl substances (PFASs) have been widely used in the production of consumer products globally due to the excellent water and oil resistance and anti-fouling properties. The multiple toxic effects of some PFASs also pose a threat to human health and ecosystem, and the frequent use of certain consumer products increased the risk of human exposure to PFASs. More data on the occurrence, concentration, and migration of PFASs in consumer products is urgently needed to address the possible risks posed by exposure to consumer products. This paper reviews the PFAS concentrations found, the migration characteristics known, and the exposure risks of PFASs arising from several types of consumer products over the last five years. The types of consumer products considered here include food contact materials, textiles, and disposable personal hygiene products. The influence of different factors on the migration process of PFASs from these products are summarized and discussed. Additionally, the main approaches and models of exposure assessment are evaluated and summarized. Current challenges and future research prospects in this field are discussed with a view to providing guidance for the future assessment and regulation of PFASs in consumer products.


How do fertility facilities in Japan perceive disclosing institutional success rates for IVF? A nationwide survey of registered assisted reproductive technology facilities

Abstract: Nationwide survey of JSOG-registered ART facilities on perceptions of disclosing institutional success rates for IVF. Provides context for the JSOG registry's reporting model and clinic-level transparency conventions.


Premature Ovarian Insufficiency: Hope for 'Failing' Ovaries

Abstract:
1. Define premature ovarian insufficiency, diagnostic criteria, risk factors and comorbidities.
2. Discuss health concerns, as well as health and hormone management of patients suffering with POI.
3. Discuss restorative fertility approaches to those with POI.


CARTR Plus 2025 Annual Report (2024 Data) - Canadian Assisted Reproductive Technologies Register

Abstract: CARTR Plus 2025 annual report covering Canadian ART activity for treatment cycles completed in 2024. Reports cycles performed, single-embryo transfer rates, clinical pregnancy and live-birth rates, ART-conceived births, and multiple-pregnancy rates from participating CFAS member ART centers. Voluntary professional-society reporting from Canadian ART clinics.

Canadian Fertility and Andrology Society - CARTR Plus


National Patient Survey 2024

National Patient Survey 2024

Human Fertilisation and Embryology Authority

Abstract:
# National Patient Survey 2024
Survey of UK fertility patients: 2 September - 9 October 2024
Published: March 2025
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/vf5bxixp/national-patient-survey-2024-underlying-dataset.xlsx "Download the underlying dataset for the ‘National Patient Survey 2024’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#introduction)
- [Section 1: Over 70% of patients were satisfied with treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-1)
- [Section 2: Almost 80% of patients spoke to a GP before treatment](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-2)
- [Section 3: 73% had used an additional test, treatment or emerging technology](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-3)
- [Section 4: Around a quarter of respondents had used donor eggs, sperm, or embryos](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-4)
- [Section 5: 40% of those able to donate would be willing to donate to research](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-5)
- [Section 6: Familiarity with the HFEA increased to 68%](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#section-6)
- [Qualitative summary](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#qualitative-summary)
- [About our data](https://www.hfea.gov.uk/about-us/publications/research-and-data/national-patient-survey-2024/#about-our-data)
## Main points
- Fertility patients’ satisfaction with most ...


Q-IVF Annual Report 2025: Fertility Treatments in Sweden (Treatment Year 2023)

Q-IVF, National Quality Registry for Assisted Reproduction

Abstract: Sweden national IVF registry report covering 2023 treatments. 26,500 treatments started at 23 clinics (6 public, 17 private). 5,804 live born children (5,508 IVF + 296 IUI-D). Fresh IVF delivery rate 27% per ET (own gametes). FET delivery rate 36.9% per ET. Cumulative delivery rate per OPU within 1 year: 45%. SET rate 97%. Multiple birth rate 1.7%. OHSS hospitalization rate 0.4%. 1,121 oocyte freezing cycles (865 social, 186 oncological). Patient satisfaction: medical care 92%, treatment 94%.


Editorial: Nervous system and reproduction: a highly integrative partnership

Abstract: Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.


Novel Approaches to Diagnosing and Treating Endometriosis

Margherita Orlandi

Private Veterinary Laboratory "MyLav," Passirana di Rho, Italy.


Theologians and Authority

Theologians and Authority

Francesca Giorgia Paleari

Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy.

Ariel Knafo-Noam

Department of Psychology, The Hebrew University of Jerusalem, Jerusalem, Israel.


Porous nickel–cobalt phosphate with oxygen-rich vacancies in situ grown on dopamine-modified cellulose textiles as self-supporting high mass loadings supercapacitor electrode

Xiaojing Hou

Nanjing Maternity and Child Health Care Hospital

Abstract: Transition-metal phosphates/phosphides showcase significant promise for energy-related applications because of their high theoretical electrochemical characteristics. However, sluggish electro/ion transfer rates and kinetically unfavorable reaction sites hinder their application at high mass loading. Herein, a self-supporting electrode based on transition-metal phosphates was successfully fabricated via a one-step electrodeposition process. The nanosheet structure of transition-metal phosphates, formed by interconnecting nanoparticles, effectively mitigates the impact of stress and achieves a high mass-loading (21 mg cm-2) of the electrode. Additionally, the oxygen vacancy-rich and porous nanostructure of transition-metal phosphates endows the as-prepared electrodes with a significantly increased conductivity and fast ion migration rate for enhancing electrochemical kinetics. Consequently, the as-fabricated transition-metal phosphate electrode displays the highest areal specific capacity of 39.2F cm-2. Furthermore, the asymmetric supercapacitor achieves a maximum energy density of 0.79 mWh cm-2 and a high capacity retention of 93.0 % for 10000 cycles under 60 mA cm-2. This work provides an ideal strategy for fabricating flexible electrodes with high mass loading and synthesizing transition-metal phosphate electrodes rich in oxygen vacancies.

Journal of Colloid and Interface Science


US fertility rate sank to new low in 2024 amid rise of pronatalism politics


Progestins in the Prevention of Preterm Birth

Shanqin Qi

The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Kehua Wang

Reproduction and Genetics Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine


The Effect of Human Peritoneal Fluid on Embryonic Development

Saadet Özen Akarca-Dizakar

Department of Histology and Embryology, Faculty of Medicine, Gazi Mustafa Kemal, İzmir Bakırçay University, 35665, Menemen, İzmir, Türkiye. ozenakarca@gmail.com.


How much does IVF cost?

How much does IVF cost?


Is termination of a desired pregnancy due to possible fetal abnormalities a case of moral injury? A preliminary report

Abstract: Termination of pregnancy (TOP) due to possible fetal abnormalities is known to be associated with various mental health problems. This study examines associations between potentially morally injurious events (PMIEs), moral injury outcomes (MI), posttraumatic stress disorder (PTSD), and prolonged grief (PG) among treatment-seeking women following late pregnancy loss. A volunteer sample of (n = 132) Israeli women who attended a reproductive psychiatry clinic following TOP (n = 99) or pregnancy loss due to intrauterine fetal demise (IUFD; n = 33), responded to self-report questionnaires in a cross-sectional, comparative study. Results show that among participants in the TOP group, PMIEs-self predicted MI outcomes of shame, and PMIEs-betrayal predicted MI outcomes of trust violation. Importantly, following exposure to PMIE-self, MI outcomes of trust violation significantly predicted both PTSD and PG symptoms. This study emphasized that TOP due to possible fetal abnormalities, may constitute a morally injurious experience, highlighting the need for clinical interventions addressing MI.


Endometriosis Quality of Life Cohort Study: Long-term Impact of Radical Laparoscopic Excision of Endometriosis

Krishnan Karthigasu

Krish Karthigasu, FRANZCOG, MBBS, MRCOG Senior lecturer, School of Women's & Infants Health, King Edward Memorial Hospital, University of Western Australia, Australia, Tel.: +61 893 828 323, Fax: +...

Gynecology and minimally invasive therapy


Mood disorders and the reproductive cycle: affective disorders during the menopause and premenstrual dysphoric disorder


Semen quality and lifespan: a study of 78,284 men followed for up to 50 years


The Ovulation Method: Ten Years of Research

Adrian Soto-Mota

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Thomas W Hilgers

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


The Emotional Aspects of Infertility: Experiences of Three Couples


Artificial insemination of single women

Artificial insemination of single women

Wenjuan Li

Ministry of Agriculture and Rural Affairs


Placental Synthesis of Steroid Hormones in Maternal-Fetal Endocrinology


The Pathology and Treatment of Leucorrhœa

Keechilat Pavithran

Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

Indhu Ramachandran Nair

Department of Pathology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

Anupama Rajanbabu

Department of Gynecologic Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.

Ajay Sasidharan

Department of Radiation Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India


The pathogenesis, diagnosis, and treatment of chronic endometritis: a comprehensive review

Abstract: Chronic endometritis (CE) is a subtle but persistent inflammatory disorder of the endometrium that is often underdiagnosed due to its asymptomatic or non-specific presentation. The etiology of CE primarily involves microbial infections and immune dysregulation, often accompanied by microbial dysbiosis. Diagnosis relies on histopathological examination, especially the identification of stromal plasma cells, alongside hysteroscopic findings and microbiological testing, though standardization remains lacking. Mechanistically, CE-induced infertility stems from altered immune cell profiles, impaired endometrial receptivity, aberrant decidualization, dysbiosis of the endometrial microbiota, and abnormal uterine peristalsis. Aberrant gene expression and hormone receptor dysregulation further disrupt the implantation window. This review summarizes current understanding of the diagnostic criteria, pathogenic mechanisms, and therapeutic strategies for CE, emphasizing its crucial role in infertility and the need for standardized clinical management.


International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2019

Abstract: ICMART world report on global assisted reproductive technology activity in 2019. Reports utilization, effectiveness, and safety data submitted from national and regional registries worldwide. Pre-pandemic activity baseline. Authors: Dyer S, Chambers GM, Jwa SC, Baker VL, Banker M, de Mouzon J, Elgindy E, Fu B, Ishihara O, Kupka M, Zegers-Hochschild F, Adamson GD.


Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization

Lin Wu

First Affiliated Hospital of Xiamen University

Abstract:
Abstract
The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.


Relationship between chronic endometritis and fallopian tube obstruction and its  influence on pregnancy outcome after fallopian tubal recanalization

D K Li

Vancouver Hospital and Health Sciences Centre

Abstract:
Background: Chronic endometritis (CE), frequently asymptomatic, is associated with female infertility. Fallopian tube obstruction (FTO) is also one of the factors contributing to female infertility. More than 90% of cases of proximal FTO can be successfully treated after fallopian tubal recanalization (FTR) and the spontaneous pregnancy rate of treated women after FTR is only about 30%. Potential factors affecting the success rate of FTR remain unclear. We speculate that CE may be one of the reasons affecting the recanalization of the fallopian tubes.

Objectives: To identify the correlation between CE and FTO, as well as the influence of CE on pregnancy outcomes following FTR.
Design: Retrospective observational study.

Methods: We retrospectively analyzed 498 women of childbearing age who underwent laparoscopy and hysteroscopy surgery for infertility. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Based on the results of the tubal patency test, they were divided into two groups: the fallopian tubal patency group and the proximal FTO group. The prevalence of CE was compared between these two groups. All women with FTO underwent FTR during the operation until successful treatment was achieved. Pregnancy outcomes were assessed after a 12-month follow-up period following the procedures. Logistic regression was used to analyze factors that might affect pregnancy after FTR.

Results: The prevalence of CE in women with tubal obstruction was 30.5%, which was significantly higher than that in the fallopian tubal patency group (10.75%), p < 0.001. After FTR, the prevalence of CE in non-pregnant women was 40.18%, which was higher than that in pregnant women (40.18% vs 13.11%), and the difference was significant (p < 0.001). Multiple regression analysis showed that CE was a significant risk factor for FTO (OR: 2.54, 95% CI: 1.368-4.717, p < 0.05). In addition, CE was identified as a risk factor for infertility after FTR (OR: 4.730, 95% CI: 2.012-11.122).

Conclusion: The presence of CE seems to decrease the likelihood of achieving spontaneous pregnancy following FTR. This observation underscores the clinical importance of early detection and treatment of CE, emphasizing the necessity for immediate intervention to prevent potential fertility complications.

Therapeutic Advances in Reproductive Health


Endometriosis and Ovarian Cancer-Reply

Endometriosis and Ovarian Cancer-Reply


Validation of administrative health data for the identification of endometriosis  diagnosis

Leslie V Farland

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

Abstract:
STUDY Question: How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?

SUMMARY ANSWER: For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.

WHAT IS KNOWN ALREADY: Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high interand intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.

STUDY DESIGN, SIZE, DURATION: In this validation study, participants (n = 412) of the Utah operative cohort of the ENDO Study (2007-2009) were linked to medical records from the Utah Population Database (UPDB) to compare endometriosis diagnoses from each source. The UPDB is a unique database containing linked data on over 11 million individuals, including statewide ambulatory and inpatient records, state vital records, and University of Utah Health and Intermountain Healthcare electronic healthcare records, capturing most Utah residents.

PARTICIPANTS/MATERIALS, SETTING, Methods: The ENDO operative cohort consisted of individuals aged 18-44 years with no prior endometriosis diagnosis who underwent gynecologic laparoscopy or laparotomy for a variety of surgical indications. In total, 173 women were diagnosed with endometriosis based on surgical visualization of disease, 35% with superficial endometriosis, 9% with ovarian endometriomas, and 14% with deep infiltrating endometriosis. Contemporary administrative health data from the UPDB included ICD diagnostic codes from Utah Department of Health in-patient and ambulatory surgery records and University of Utah and Intermountain Health electronic health records.

MAIN RESULTS AND THE ROLE OF CHANCE: For endometriosis diagnosis, we found relatively high sensitivity (0.88) and specificity (0.87) and substantial agreement (Kappa [Κ] = 0.74). We found similarly high sensitivity, specificity, and agreement for superficial endometriosis (n = 143, 0.86, 0.83, Κ = 0.65) and ovarian endometriomas (n = 38, 0.82, 0.92, Κ = 0.58). However, deep infiltrating endometriosis (n = 58) had lower sensitivity (0.12) and agreement (Κ = 0.17), with high specificity (0.99).

LIMITATIONS, REASONS FOR CAUTION: Medication prescription data and unstructured data, such as clinical notes, were not included in the UPDB data used for this study. These additional data types could aid in detection of endometriosis. Most participants were white or Asian with Hispanic ethnicity reported 11% of the time, which may limit generalizability to some US states. Additionally, given that participants whose administrative health records we utilized were also part of the ENDO Study, the surgeons may have been more vigilant in diagnostic coding due to the operative forms they completed for the ENDO Study, which may have led to increased validity. However, the codes compared in the UPDB would have been entered by medical coders as part of standard clinical practice.

WIDER IMPLICATIONS OF THE Findings: We observed substantial agreement between administrative health data and surgically confirmed endometriosis diagnoses overall, and for superficial and ovarian endometrioma subtypes. These findings may provide reassurance to researchers using administrative healthcare records to assess risk factors and long-term health outcomes of endometriosis. Our findings corroborate prior research that demonstrates high specificity but low sensitivity for deep infiltrating endometriosis, indicating deep infiltrating endometriosis is not reliably annotated in administrative healthcare data. This suggests that medical record-based deep infiltrating endometriosis diagnoses may be suitable for etiologic studies but not for surveillance or detection studies. STUDY FUNDING/COMPETING INTEREST(S): The original ENDO Study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). We acknowledge partial support for the UPDB through grant P30 CA2014 from the National Cancer Institute, University of Utah and from the University of Utah's program in Personalized Health and Center for Clinical and Translational Science. This research was also supported by the NCRR grant, 'Sharing Statewide Health Data for Genetic Research' (R01 RR021746, G. Mineau, PI) with additional support from the Utah Department of Health and Human Services, University of Utah. Additionally, this research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Centers for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP007131, with additional support from the University of Utah and Huntsman Cancer Foundation. Research reported in this publication was also supported by the National Institutes of Health (Award Numbers R01HL164715 [to L.V.F., K.C.S., and A.Z.P.] and K01AG058781 [to K.C.S.]), by the Huntsman Cancer Institute's Breast and Gynecologic Cancers Center, and by the Doris Duke Foundation's COVID-19 Fund to Retain Clinical Scientists funded by the American Heart Association. A.C.K. was supported by Training Grant Number 5T15LM007124 from the National Library of Medicine to K.E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other sponsors. There are no competing interests among any of the authors.

TRIAL REGISTRATION NUMBER: N/A.


Lab-based semen parameters as predictors of long-term health in men-a systematic  review

Abstract:
STUDY Question: Can semen parameters predict long-term health outcomes in men?

SUMMARY ANSWER: There is a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration.

WHAT IS KNOWN ALREADY: Male infertility has been long associated with a higher mortality risk and possibly higher chance of developing comorbidities but there has been less focus on semen analysis as a potential predictive factor. STUDY DESIGN SIZE DURATION: We searched PubMed/MEDLINE, EMBASE, and EBM databases from inception to December 2023. MESH term strategy: heading 1 ('OR', semen analysis, sperm count, sperm parameter*, male infertility, azoospermia, aspermia, oligospermia, teratozoospermia, asthenozoospermia) 'AND' heading 2 ('OR', morbidity, mortality, diabetes, cancer, cardiovascular, death, hypertension, stroke, long-term health). We included all studies that analyzed the risk of mortality and/or future development of comorbidities in men with at least one semen analysis. Case series and reviews were excluded. PARTICIPANTS/MATERIALS SETTING

Methods: A narrative synthesis was done for all studies and meta-analysis where possible. Odds ratio (ORs) (95% CI, P-value) were calculated for all men with one suboptimal semen parameter and associated with the risk of a particular outcome. The risk of bias was assessed with QUADAS-2.

MAIN RESULTS AND THE ROLE OF CHANCE: Twenty-one studies were finally included. There was either a high or unclear risk of bias in all studies. The results only allowed for meta-analysis on categories of sperm concentration. We found a 2-fold increase in mortality risk in azoospermic men compared to oligospermic (OR 1.96, 95% CI: 1.29-2.96) and normozoospermic (OR 2.00, 95% CI: 1.23-3.25) groups, but not in oligospermic compared to normozoospermic (OR 1.04, 95% CI: 0.52-2.09). There was no difference in risk of cardiovascular disease in any of the sperm concentration groups (azoospermic-oligospermic OR 0.94, 95% CI: 0.74-1.20, azoospermic-normozoospermic OR 1.11, 95% CI: 0.71-1.75, and oligospermic-normozoospermic OR 1.12, 95% CI: 0.80-1.55). OR for diabetes in azoospermic men was higher only compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01). The risk of all-site cancer was higher in azoospermic men compared to oligospermic (OR 2.16, 95% CI: 1.55-3.01) and normozoospermic (OR 2.18, 95% CI: 1.20-3.96). Only azoospermic men might be at higher risk of testicular cancer when compared to men with normal sperm concentration (OR 1.80, 95% CI: 1.12-2.89). LIMITATIONS REASONS FOR CAUTION: Although our pooled analysis shows an increased risk of mortality and all-site cancer risk in azoospermic men, the results show a lack of evidence to suggest a higher risk of comorbidities in men with poor semen concentration. Given the limited available data, the nature of the studies, and the high risk of bias, the results should be interpreted with caution.

WIDER IMPLICATIONS OF THE Findings: There is not enough data to confirm the usability of semen analysis as a predictor of poor long-term health in men, especially within the general population.

STUDY FUNDING/COMPETING INTERESTS: No funding was obtained for this study. A.M. has received funding from Merck Serono, Ferring, Gedeon Richter, Pharmasure, and Cook Medical to attend medical conferences; has been a participant in an advisory board for Ferring; and has given an invited lecture for a Merck Serono advisory board. S.N. has received funding for medical conference attendance from Ferring and Cook Medical. REGISTRATION NUMBER: PROSPERO No. CRD42024507563.


Current surgical treatment of uterine isthmocele: an update of existing  literature

Abstract: The prevalence of uterine isthmocele, also known as a uterine niche, has risen in parallel with increasing cesarean section (CS) rates, affecting approximately 60% of women depending on their history of cesarean deliveries. This condition, now categorized as cesarean scar disorder (CSD) by the "Delphi consensus," is characterized by one primary or two secondary symptoms. Diagnosis can be made through transvaginal ultrasound, sonohysterography, hysteroscopy, or magnetic resonance imaging (MRI). Management of isthmocele may involve pharmacological or surgical interventions. This review aims to provide a thorough analysis of the surgical management options, focusing on postoperative symptom relief, intraoperative and postoperative complications, length of hospital stay, and impact on secondary infertility. PubMed was comprehensively searched for observational studies from inception to 07.08.2024. Surgical treatments include hysteroscopic resection, laparoscopic procedures, and vaginal approaches, all of which offer comparable symptom relief. However, the vaginal approach is associated with a longer hospital stay. The robotic-assisted approach shows promising results but lacks extensive data. Among surgical options, hysteroscopic treatment has the fewest complications but is generally avoided when residual myometrial thickness (RMT) is less than 3 mm. While many CSDs remain asymptomatic, and some women with uterine isthmocele may not wish to conceive, symptomatic patients or those desiring to conceive may benefit from surgical intervention. The choice of procedure should be based on individual patient characteristics, particularly RMT, to define the most appropriate surgical approach.


Maternal use of hormonal contraception and risk of childhood leukemia: A  Scandinavian population-based cohort study

Susanne K Kjaer

Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark; Department of Gynaecology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: susanne@...

Justine Bénévent

Centre Hospitalier Universitaire de Toulouse

Maarit K Leinonen

Finnish Institute for Health and Welfare

Abstract:
Background: Maternal hormonal contraception use has been associated with childhood leukemia risk. However, studies are few and often based on self-reported information.

Methods: Using registry data from Denmark, Norway, and Sweden, we identified 3,183,316 children (born 1996-2018) and followed them from birth until leukemia diagnosis, censoring (death, emigration, other cancer, 20th birthday) or study closure (December 31st, 2017, 2018 or 2020). We estimated hazard ratios (HRs) and 95 % confidence intervals (CIs) for childhood leukemia (any, lymphoid and non-lymphoid) associated with maternal recent use (≤ 3 months before or during pregnancy) or previous use (before recent use) of hormonal contraception overall and by type, compared to no use.

Results: During 29,455,528 person-years, 1701 children developed leukemia (no use: 518, previous use: 974, recent use: 209). Maternal recent use of hormonal contraception was associated with an increased leukemia risk in children (HR 1.22, 95 % CI 1.04-1.44; incidence rate per 1,000,000 person-years [IR] 65), compared to no use (IR 53). The association was strongest for non-lymphoid leukemia (HR 1.69, 95 % CI 1.20-2.37) and mainly driven by the oral combined products, both for any leukemia (HR 1.29, 95 % CI 1.05-1.59) and non-lymphoid leukemia (HR 1.75, 95 % CI 1.17-2.62). Additionally, non-lymphoid leukemia was associated with recent use of the non-oral progestin-only products (HR 2.10, 95 % CI 1.28-3.44).

Conclusions: Although the absolute risk was low, maternal hormonal contraception use up to or during pregnancy was associated with an increased childhood leukemia risk, particularly non-lymphoid leukemia, and mainly driven by oral combined and non-oral progestin-only products.

European Journal of Cancer (Oxford, England : 1990)


Editorial: Opportunities and challenges of human preconception research

Gita D Mishra

School of Public Health University of Queensland Herston QLD Australia

Evelyn Loo

Institute of Human Development and Potential (A*STAR) and Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.


Evidence-based guideline: premature ovarian insufficiency

Panay N, Anderson RA, Bennie A, Cedars M, Davies M, Ee C, Gravholt CH, Kalantaridou S, Kallen A, Kim KQ, Misrahi M, Mousa A, Nappi RE, Rocca WA, Ruan X, Teede H, Vermeulen N, Vogt E, Vincent AJ, ESHRE, ASRM, CREWHIRL, and IMS Guideline Group on POI

Abstract:
Study question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?Summary answerThe current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI.

What is known already: Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.Study design size durationThe guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessments were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials (RCTs) on POI included in the guideline.

Participants/materials setting methodsBased on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee.

Main result: s and the role of chanceNew data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH >25 IU is required for diagnosis of POI, and guidance that AMH testing, repeat FSH measurement, and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care.

Limitations reasons for cautionThe guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI.

Wider implication: s of the findingsThe guideline provides health care professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.Study funding/competing interestsThe guideline was developed and funded by ESHRE, American Society for Reproductive Medicine (ASRM), Centre for Research Excellence in Women's Health in Reproduction Life (CRE-WHiRL), and International Menopause Society (IMS), covering expenses associated with the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive payments. N.P. declared grants from Bayer Pharma (research and consultancy) and NIHR-research POISE; consulting fees from Abbott, Astellas, Bayer, Besins, Lawley, Mithra, Theramex, Viatris; honoraria from Astellas, Bayer, Besins, Gedeon Richter, Theramex, Viatris; support for attending meetings and/or travel from Astellas, Bayer, Theramex, Viatris; President, International Menopause Society, Medical Advisory Committee member, British Menopause Society, Patron Daisy Network. A.J.V. declared grants from Amgen Australia, Australian NHMRC, and Australian MRFF; consulting fees from IQ Fertility; honoraria from the Australasian Menopause Society; participation on a Data Safety Monitoring Board or Advisory Board of Astellas; Board Member of the International Menopause Society (2020 to current) and Past president of the Australasian Menopause Society (2017-2019); R.A.A. declared grants from Roche (Research support, to institution), and participation on a Data Safety Monitoring Board of Bayer. M.C. declared grants from NHI; payments or honoraria from Up-to-Date (as editor/reviewer); Board Member of American Society of Reproductive Medicine, and of American Gynecological and Obstetrical Society. M.D. declared (NIHR-HTA Reference Number: NIHR133461; NIHR-HTA Reference Number: NIHR128757; Action Medical Research and Borne: GN2818) consulting fees from a small personal medical practice, support for attending meetings and/or travel from ESHRE, Bayer and UCLH special Trustees; Participation on the Advisory Board of the British Menopause Society, UKSTORE project, the Progress Educational Trust, and the Turner Syndrome Support Society UK; Leadership or fiduciary roles in the British Fertility Society (Trustee), Elizabeth Garrett Anderson Hospital Charity (chair of Trustees), and the Essex Wynter charitable trust (Trustee). C.E. declared being Chair of a SIG from the Royal Australian College of General Practitioners Integrative Medicine Specific Interest Group and Program Lead for Next Practice Western Sydney Integrative Health. C.H.G. declared grants from Novo Nordisk Foundation (Nos. NNF15OC0016474 and NNF20OC0060610), sygesikringen danmark (No 2022-0189), and the Independent Research Fund Denmark (Nos. 0134-00406 and 0134-00130B); consulting fees from Novo Nordisk, Merck, and Astra Zeneca. S.K. declared grants from Roche diagnostics. A.K. declared grants from NIH R01 5R01HD101475; consulting fees as Medical Reviewer for Flo and for Healthline; honoraria as Medical Consultant for Summus; support for attending meetings from the Reproductive Scientist Development Program; Society for Reproductive Investigation Council Member and Society for Assisted Reproduction Registry/Validation Chair; R.E.N. declared consulting fees from Astellas, Bayer Pharma, Besins Healthcare, Fidia, Theramex; honoraria from Abbott, Astellas, Exeltis, Fidia, Gedeon Richter, Merck & Co, Novo Nordisk, Shionogi Limited, Theramex, Viatris; payment for expert testimony from Vichy Laboratories; Participation in Data Safety Monitoring Board of Advisory board from Astellas and Bayer Healthcare; President elect of the International Menopause Society (IMS). H.T. declared a grant from NHMRC Centre for Research Excellence for women's health in reproductive life. A.B. declared being chair of the Daisy Network Charity. The other authors have no conflicts of interest to declare.DisclaimerThis guideline represents the views of ESHRE, ASRM, CRE-WHiRL, and IMS, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. The collaborating societies make no warranty, expressed or implied, regarding the clinical practice guidelines and specifically exclude any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.).


Evidence-based guideline: premature ovarian insufficiency(†)(‡)

Panay N, Anderson RA, Bennie A, Cedars M, Davies M, Ee C, Gravholt CH, Kalantaridou S, Kallen A, Kim KQ, Misrahi M, Mousa A, Nappi RE, Rocca WA, Ruan X, Teede H, Vermeulen N, Vogt E, Vincent AJ

Abstract:
STUDY Question: How should premature/primary ovarian insufficiency (POI) be diagnosed and managed, based on the best available evidence from published literature?

SUMMARY ANSWER: The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae and treatment of POI.

WHAT IS KNOWN ALREADY: POI presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life, on fertility and on bone, cardiovascular and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.

STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development of European Society of Human Reproduction and Embryology (ESHRE) guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and healthcare professionals. Literature searches and assessment were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials on POI included in the guideline.

PARTICIPANTS/MATERIALS, SETTING, Methods: Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee.

MAIN RESULTS AND THE ROLE OF CHANCE: New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help healthcare professionals apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated follicle stimulating hormone (FSH) >25 IU is required for diagnosis of POI and guidance that AMH testing, repeat FSH measurement and/or AMH may be required where there is diagnostic uncertainty. Recommendations were also updated regarding genetic testing, estrogen doses and regimens, use of the combined oral contraceptive and testosterone therapy. Women with lived experience of POI informed the recommendations on provision of care.

LIMITATIONS, REASONS FOR CAUTION: The guideline describes different management options, but it must be acknowledged that for most of these options, supporting evidence is limited for POI.

WIDER IMPLICATIONS OF THE Findings: The guideline provides healthcare professionals with clear advice on best practice in POI care, based on the best evidence currently available. In addition, a list of research recommendations is provided to guide further studies in POI.

Climacteric : the Journal of the International Menopause Society


Ischemic Stroke in Users of Combined Hormonal Contraceptives: A Danish Registry  Study

Klaus Kaae Andersen

Kjobenhavns Telefon Aktieselskab (Denmark)

Abstract:
Background: The combined hormonal contraceptive (CHC) with ethinylestradiol and progestins is the most widely used contraceptive method among young women and is used by millions worldwide. However, uncertainties exist about the risk of ischemic stroke associated with the use of CHCs with low-dose ethinylestradiol (<50-µg ethinylestradiol) and with the newest fourth-generation progestins that have only been sparsely investigated for the risk of ischemic stroke.

Methods: In this cohort study based on Danish registries covering the entire Danish female population aged 18 to 49 years from 2004 to 2021, we investigated incidence rate ratios (IRRs) of ischemic stroke using CHCs compared with nonuse of hormonal contraceptives. Analyses focused on comparing CHCs based on ethinylestradiol content (30-40versus ≤20-μg ethinylestradiol), progestin generation (second, third, and fourth) in CHCs, and route of administration (monophasic versus sequential). Poisson regression models adjusting for age, education, ethnicity, calendar year, and medication used for risk factors were utilized.

Results: In total, 1 711 757 nonpregnant women contributed 14 697 788 person-years to the investigation. For users of CHCs containing <50-µg ethinylestradiol, the adjusted IRR was increased by 1.77 (95% CI, 1.62-1.93) compared with nonusers of hormonal contraceptives. IRR did not differ between CHCs with 30to 40and ≤20-µg ethinylestradiol. Adjusted incidence rate difference between CHC users and nonusers of hormonal contraceptives ranged from 1 in 100 000 women per year in 18 to 24 years of age to 24 in 100 000 women per year in ≥45 years of age. Incidence rate in users of fourth-generation CHCs was 30% lower than that of second-generation CHCs adjusted IRR (0.70 [95% CI, 0.50-0.98]). IRR for users of third-generation CHCs did not differ significantly from that of second-generation users adjusted IRR (1.14 [95% CI, 0.97-1.35]).

Conclusions: Use of CHCs was associated with a 1.77 higher IRR of ischemic stroke. IRR did not relate to ethinylestradiol content in users of CHCs with <50-µg ethinylestradiol. IRR was 30% lower in users of fourth-generation than in users of second-generation CHCs.


Using anti-Müllerian hormone to predict premature ovarian insufficiency: a  retrospective cross-sectional study

Abstract:
Background: Premature ovarian insufficiency/failure (POI/POF) is a significant issue for women of reproductive age. Anti-Müllerian hormone (AMH) is a potential biomarker of ovarian reserve, but its clinical value in diagnosing and predicting POI/POF remains unclear. This study aimed to analyze the correlation between AMH and basal follicle-stimulating hormone (FSH) levels in women aged 18 to 40 and evaluate AMH's predictive value for POI/POF.

Methods: A total of 21,143 participants aged 18-40 who visited the gynecology department or underwent physical examinations at the International Peace Maternity and Child Health Hospital in Shanghai, China, from July 2016 to June 2021 were enrolled. Demographic information and laboratory test results were collected, including age, FSH, AMH, E2 and test dates. Participants were grouped by FSH and AMH levels, and subgroup analyses were performed to investigate the relationship between these hormones and age. The AMH level associated with POI risk was evaluated using restricted cubic splines (RCS) and logistic regression. Clinical benefit was assessed by decision curve analysis (DCA).

Results: Participants with higher FSH levels had significantly lower median AMH levels and vice versa(p<0.001). At AMH ≥ 0.5 ng/mL, FSH levels were normal or slightly elevated with age. At AMH level below 0.5ng/ml,basal FSH increased significantly with age. At FSH <10 IU/L, AMH levels show a trend of rising and then decreasing with age, reaching a peak at approximately 25 years old and gradually decreasing with age. At FSH ≥10 IU/L, AMH levels show a gradual downward trend with age, and at FSH >40 IU/L, AMH levels remain very low to undetectable values. The RCS showed that the risk of POI/POF in the overall population sharply increased until serum AMH reached a low level (below 0.5ng/ml). DCA showed that a low AMH level had good clinical diagnostic utility in predicting POI/POF.

Conclusion: Our analysis of a large dataset suggests that serum AMH levels are inversely correlated with FSH levels and that AMH is a good predictor of POI until it drops to a low level.


RTAC Code of Practice for Reproductive Technology Units (Australia and New Zealand) - December 2024 (Issue 9)

Reproductive Technology Accreditation Committee

Abstract: RTAC Code of Practice (Issue 9) governing accreditation requirements for reproductive technology units operating in Australia and New Zealand. Sets standards for clinical, laboratory, and quality-management practices that ART centres must meet to remain RTAC-accredited and eligible to submit cycles to ANZARD. Includes patient safety, embryology laboratory, donor-program, and incident-reporting requirements. Effective from December 2024.

Fertility Society of Australia and New Zealand - RTAC


Recognizing Endometrial Cancer Risks in Perimenopausal and Postmenopausal Experiences: Insights From Community Qualitative Interviews and Workshop

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Objectives: To evaluate the experiences of perimenopausal and postmenopausal women in British Columbia, their perceptions of expected reproductive aging, and potential concerns about endometrial cancer (EC).

Methods: We interviewed 31 midlife community women of diverse backgrounds and hosted a workshop for more in-depth discussion. We summarized relayed experiences and beliefs through a thematic and descriptive analysis of participant stories and workshop feedback.

Results: Participants demonstrated a somewhat simplistic understanding of midlife changes, facing this phase of life with a "tough-it-out" attitude rather than seeking medical help for arising symptoms. Awareness of EC and EC-specific risk factors, such as obesity, was low. Confusion between cervical and EC was common. Although abnormal bleeding was seen as potentially of concern, many opted to wait before seeking medical help. Workshop participants stressed the need to include awareness about EC in a broader conversation about perimenopause and menopause and suggested strategies for disseminating EC awareness.

Conclusions: Community women in British Columbia demonstrated low awareness of EC-associated symptoms and risk factors. There is little information to help distinguish when perimenopausal abnormal uterine bleeding is of concern and when to seek help. This highlights the need to enhance knowledge of EC and its risk factors in perimenopause among the public and among health care providers.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC


Family Formations in Fertility Treatment 2022

Human Fertilisation and Embryology Authority

Abstract:
# Family formations in fertility treatment 2022
Preliminary UK family type statistics for IVF and DI treatment, storage, and donation
Published: November 2024
[Download the underlying dataset as .xlsx](https://www.hfea.gov.uk/media/zpjlvhnd/family-formations-in-fertility-treatment-2022-underlying-dataset.xlsx "Download the underlying dataset for the ‘Family formations in fertility treatment 2022’ report")
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#main-points)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#introduction)
- [Section 1: The proportion of female same-sex couples and single patients having fertility treatment has changed](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-1)
- [Section 2: IVF birth rates highest among female same-sex couples](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-2)
- [Section 3: Single patients are starting IVF younger than previous years](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-3)
- [Section 4: Patient population changes between those storing eggs and thawing them](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-4)
- [Section 5: Average IVF multiple birth rate decreased across all family types](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-5)
- [Section 6: Female same-sex couples and single patients had the lowest levels of NHS funding](https://www.hfea.gov.uk/about-us/publications/research-and-data/family-formations-in-fertility-treatment-2022/#section-6)
- [Section 7: Up to two-thirds o...


Is Vaginal Repair a Good Option for Severe Cesarean Scar Defect? Comparison of  Women With or Without Residual Myometrium

Perrine Capmas

Department of Gynecology and Obstetrics, Bicetre Hospital, Le Kremlin Bicetre, France (all authors); Faculty of Medicine, University Paris Saclay, Le Kremlin Bicetre, France (Drs. Fernandez and Cap...

Abstract:
STUDY Objective: To compare outcomes of vaginal surgery in women with moderate or severe symptomatic cesarean scar defect (with or without residual myometrium).
Design: Retrospective cohort study.
Setting: Gynecology department of a teaching hospital.

Patients: Fifty-three women, between January 2014 and December 2019, underwent vaginal surgery for symptomatic cesarean scar defect: 20 women with moderate defect (with residual myometrium) and 33 with severe defect (without residual myometrium).

Interventions: Vaginal surgical approach to repair cesarean scar defect. MEASUREMENTS AND

MAIN Results: surgery by comparing the myometrial residual thickness before and after surgery. The secondary objectives were evaluation of vaginal surgery efficacy on symptoms resolution, per and postoperative courses, and subsequent fertility. Failure rate was evaluated as the need for a second surgery. After vaginal surgery, the residual myometrium significantly increased from 2.4 mm ± 0.9 mm to 6.6 mm ± 2.4 mm (p <.01) in the moderate group and from 0 mm to 4.4 mm ± 2.2 mm (p <.01) in the severe group. The prevalence of abnormal uterine bleeding was significantly reduced after surgery in both groups (p <.01). Pelvic pain was significantly reduced only in the moderate group (p <.01). The rate of complications (5% vs 9.1%) and second surgery (15% vs 24.2%) were not significantly different between moderate and severe groups, respectively. The median time to conceive (7 months vs 12 months); pregnancy rates (84.6% vs 68.2%); and live birth rates (76.9% vs 50%) were not statistically significant in the moderate and severe groups respectively, with 90% of pregnancies occurring naturally. Women delivered by cesarean section at 38 weeks of gestation in both groups, and no uterine rupture was reported.

Conclusion: Despite the absence of residual myometrium, vaginal repair of severe cesarean scar defect was effective in increasing myometrial thickness, in relieving bleeding symptoms, and in allowing to achieve pregnancy.

Journal of Minimally Invasive Gynecology


Case Series: Diagnosis and Treatment of Four Rare Cancers by a Single Surgeon Due to Systematic Mapping and Near Contact Techniques

Abstract: No standard criteria exist for how to perform a diagnostic laparoscopy. This case series provides evidence of the importance of standardized, reproducible techniques. A single non-oncologic gynecologic surgeon used Near-Contact Laparoscopy (NCL) and Systematic Mapping of the Abdomen and Pelvis (S-MAP) techniques, resulting in the incidental finding and curative treatment of 4 rare cancers over 3 years. Three were neuroendocrine tumors of the appendix (incidence 0.95/100,000; probability of 3 by one surgeon: 0.0000000001). The fourth was a 2 mm well-differentiated papillary mesothelioma (WDPM). All 4 were cured. 3 of 3 infertile patients subsequently achieved pregnancy. The NCL technique was originally coined by Dr. Redwine (PMID: 3190209). The S-MAP method was described in the NaProTechnology textbook by Dr. Thomas Hilgers, and the S-MAP term coined by this author. Case D used robotic-assisted laser excision. Standardization should be incorporated as the gold standard.


Additives in Processed Foods as a Potential Source of Endocrine-Disrupting Chemicals: A Review

Abstract: Processed foods, accounting for most consumable food categories today, contain considerable amounts of food additives. Food additives are substances added to food products to improve taste, consistency, appearance, or shelf life. Various food additives, such as phthalates, bisphenol A, tartrazine, erythrosine, artificial sweeteners, and parabens, have been identified as potential sources of endocrine-disrupting chemicals (EDCs) in processed foods. EDCs are substances that frequently interfere with the regular functioning of the endocrine system, creating an unusual environment in the biological system, which leads to adverse health effects such as the disruption of hormone synthesis, receptor binding, and signal transduction pathways, as well as energy metabolic homeostatic disorders which potentially increasing the risk of obesity, type-2 diabetes, cardiometabolic diseases and may also trigger allergic reactions. Consequently, they can also impact mammary gland development, and reproductive function, further leading to developmental abnormalities. This review aims to insights into the various food additives that act as potential endocrine-disrupting chemicals (EDCs) and to describe their applications in the food industry, as well as the failure of hormonal homeostatic mechanisms, which eventually result in hazardous health effects. It also outlines strategies to reduce the use of food additives and suggests alternative additives with minimal or no endocrine-disrupting properties, highlighting their importance for maintaining human health.


Ovarian reserve does not influence natural conception: insights from infertile women

Marco Reschini

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Abstract:
PURPOSE: There is several albeit not univocal evidence suggesting that ovarian reserve is not related to the chance of natural pregnancy, provided that the remnant follicular pool is sufficient to ensure regular menstrual cycles. Nevertheless, available studies have some methodological limitations, and the issue cannot be considered definitively ascertained.

METHODS: To further address this issue, we retrospectively selected infertile women whose infertility diagnostic work-up was unremarkable (unexplained infertility-cases) and matched them by age and study period to a group of infertile women who were diagnosed with severe male infertility (controls). If ovarian reserve impacts on natural fertility, one had to expect lower ovarian reserve among women with unexplained infertility. Tested biomarkers included AMH, AFC and day 2-3 serum FSH. The primary aim was the frequency of women with serum AMH < 0.7 ng/ml.

RESULTS: Two-hundred fifty-two women with unexplained infertility and 252 women with male infertility were included. All biomarkers of ovarian reserve did not differ between the study groups. AMH levels < 0.7 ng/mL were observed in 26 (10%) women with unexplained infertility and 35 (14%) women with male infertility (p = 0.28). The adjusted OR was 0.76 (95% CI: 0.44-1.33). Significant differences did not also emerge when repeating this dichotomous analysis using other biomarkers and other thresholds for the definition of low-ovarian reserve.

CONCLUSION: This study confirms that ovarian reserve is unremarkable to natural conception. Physicians and patients should be aware of this concept to avoid inappropriate counseling and undue clinical decisions.