Next steps towards AMH as a robust biomarker for assessing ovarian aging in individual women

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Change in Androgenic Status and Cardiometabolic Profile of Middle-Aged Women with Polycystic Ovary Syndrome

Understanding the cardiovascular disease (CVD) risk for women with polycystic ovary syndrome (PCOS) at reproductive age is crucial. To investigate this, we compared the cardiometabolic profiles of different PCOS groups over a median interval of 15.8 years. The study focused on three groups: (1) women with PCOS who were hyperandrogenic at both initial and follow-up screening (HA-HA), (2) those who transitioned from hyperandrogenic to normoandrogenic (HA-NA), and (3) those who remained normoandrogenic (NA-NA). At initial and follow-up screenings, both HA-HA and HA-NA groups showed higher body mass indexes compared to the NA-NA group. Additionally, at follow-up, the HA-HA and HA-NA groups exhibited higher blood pressure, a higher prevalence of hypertension, elevated serum triglycerides and insulin levels, and lower levels of HDL cholesterol compared to the NA-NA group. Even after adjusting for BMI, significant differences persisted in HDL cholesterol levels and hypertension prevalence among the groups (HA-HA: 53.8%, HA-NA: 53.1%, NA-NA: 14.3%, p &lt; 0.01). However, calcium scores and the prevalence of coronary plaques on CT scans were similar across all groups. In conclusion, women with PCOS and hyperandrogenism during their reproductive years exhibited an unfavorable cardiometabolic profile during their post-reproductive years, even if they changed to a normoandrogenic status.</p

Change in Androgenic Status and Cardiometabolic Profile of Middle-Aged Women with Polycystic Ovary Syndrome

Understanding the cardiovascular disease (CVD) risk for women with polycystic ovary syndrome (PCOS) at reproductive age is crucial. To investigate this, we compared the cardiometabolic profiles of different PCOS groups over a median interval of 15.8 years. The study focused on three groups: (1) women with PCOS who were hyperandrogenic at both initial and follow-up screening (HA-HA), (2) those who transitioned from hyperandrogenic to normoandrogenic (HA-NA), and (3) those who remained normoandrogenic (NA-NA). At initial and follow-up screenings, both HA-HA and HA-NA groups showed higher body mass indexes compared to the NA-NA group. Additionally, at follow-up, the HA-HA and HA-NA groups exhibited higher blood pressure, a higher prevalence of hypertension, elevated serum triglycerides and insulin levels, and lower levels of HDL cholesterol compared to the NA-NA group. Even after adjusting for BMI, significant differences persisted in HDL cholesterol levels and hypertension prevalence among the groups (HA-HA: 53.8%, HA-NA: 53.1%, NA-NA: 14.3%, p < 0.01). However, calcium scores and the prevalence of coronary plaques on CT scans were similar across all groups. In conclusion, women with PCOS and hyperandrogenism during their reproductive years exhibited an unfavorable cardiometabolic profile during their post-reproductive years, even if they changed to a normoandrogenic status

Incidental findings on coronary computed tomography in women with selected reproductive disorders

OBJECTIVE: To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45–55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE). METHODS: A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients’ records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV. RESULTS: In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women. CONCLUSION: Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up

Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.&lt;p&gt;&lt;/p&gt; Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.&lt;p&gt;&lt;/p&gt; Setting: European clinical gynecology centers.&lt;p&gt;&lt;/p&gt; Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.&lt;p&gt;&lt;/p&gt; Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.&lt;p&gt;&lt;/p&gt; Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.&lt;p&gt;&lt;/p&gt; Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.&lt;p&gt;&lt;/p&gt; Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids

Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature

BACKGROUND: Family-planning policies have focused on contraceptive approaches to avoid unintended pregnancies, postpone, or terminate pregnancies and mitigate population growth. These policies have contributed to significantly slowing world population growth. Presently, half the countries worldwide exhibit a fertility rate below replacement level. Not including the effects of migration, many countries are predicted to have a population decline of >50% from 2017 to 2100, causing demographic changes with profound societal implications. Policies that optimize chances to have a child when desired increase fertility rates and are gaining interest as a family-building method. Increasingly, countries have implemented child-friendly policies (mainly financial incentives in addition to public funding of fertility treatment in a limited number of countries) to mitigate decreasing national populations. However, the extent of public spending on child benefits varies greatly from country to country. To our knowledge, this International Federation of Fertility Societies (IFFS) consensus document represents the first attempt to describe major disparities in access to fertility care in the context of the global trend of decreasing growth in the world population, based on a narrative review of the existing literature. OBJECTIVE AND RATIONALE: The concept of family building, the process by which individuals or couples create or expand their families, has been largely ignored in family-planning paradigms. Family building encompasses various methods and options for individuals or couples who wish to have children. It can involve biological means, such as natural conception, as well as ART, surrogacy, adoption, and foster care. Family-building acknowledges the diverse ways in which individuals or couples can create their desired family and reflects the understanding that there is no one-size-fits-all approach to building a family. Developing education programs for young adults to increase family-building awareness and prevent infertility is urgently needed. Recommendations are provided and important knowledge gaps identified to provide professionals, the public, and policymakers with a comprehensive understanding of the role of child-friendly policies. SEARCH METHODS: A narrative review of the existing literature was performed by invited global leaders who themselves significantly contributed to this research field. Each section of the review was prepared by two to three experts, each of whom searched the published literature (PubMed) for peer reviewed full papers and reviews. Sections were discussed monthly by all authors and quarterly by the review board. The final document was prepared following discussions among all team members during a hybrid invitational meeting where full consensus was reached. OUTCOMES: Major advances in fertility care have dramatically improved family-building opportunities since the 1990s. Although up to 10% of all children are born as a result of fertility care in some wealthy countries, there is great variation in access to care. The high cost to patients of infertility treatment renders it unaffordable for most. Preliminary studies point to the increasing contribution of fertility care to the global population and the associated economic benefits for society. WIDER IMPLICATIONS: Fertility care has rarely been discussed in the context of a rapid decrease in world population growth. Soon, most countries will have an average number of children per woman far below the replacement level. While this may have a beneficial impact on the environment, underpopulation is of great concern in many countries. Although governments have implemented child-friendly policies, distinct discrepancies in access to fertility care remain

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40Â&nbsp;years). Intervention(s) Follitropin delta (AMH &lt;15 pmol/L: 12Â&nbsp;μg/d; AMH â¥15 pmol/L: 0.10â0.19Â&nbsp;μg/kg/d; maximum 12Â&nbsp;μg/d), or follitropin alfa (150 IU/d for 5Â&nbsp;days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH &lt;15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6Â&nbsp;μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

Cardiovascular RiskprofilE - IMaging and gender-specific disOrders (CREw-IMAGO): Rationale and design of a multicenter cohort study

Background: Reproductive disorders, such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and hypertensive pregnancy disorders (HPD) like pre-eclampsia (PE), are associated with an increased risk of cardiovascular disease (CVD). Detection of early signs of cardiovascular disease (CVD), as well as identification of risk factors among women of reproductive age which improve cardiovascular risk prediction, is a challenge and current models might underestimate long-term health risks. The aim of this study is to assess cardiovascular disease in patients with

The cardiovascular risk profile of middle-aged women with polycystic ovary syndrome

Objectives: Contradictory results have been reported regarding the association between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD). We assessed the cardiometabolic phenotype and prevalence of CVD in middle-aged women with PCOS, compared with age-matched controls from the general population, and estimated 10-year CVD risk and cardiovascular health score. Design: A cross-sectional study. Participants: 200 women aged >45 with PCOS, and 200 age-matched controls. Measurements: Anthropometrics, insulin, lipid levels, prevalence of metabolic syndrome and type II diabetes. Ten-year Framingham risk score and the cardiovascular health score were calculated, and carotid intima-media thickness (cIMT) was measured. Results: Mean age was 50.5 years (SD = 5.5) in women with PCOS and 51.0 years (SD = 5.2) in controls. Increased waist circumference, body mass index and hypertension were more often observed in women with PCOS (P <.001). In women with PCOS, the prevalence of type II diabetes and metabolic syndrome was not significantly increased and lipid levels were not different from controls. cIMT was lower in women with PCOS (P <.001). Calculated cardiovascular health and 10-year CVD risk were similar in women with PCOS and controls. Conclusions: Middle-aged women with PCOS exhibit only a moderately unfavourable cardiometabolic profile compared to age-matched controls, even though they present with an increased BMI and waist circumference. Furthermore, we found no evidence for increased (10-year) CVD risk or more severe atherosclerosis compared with controls from the general population. Long-term follow-up of women with PCOS is necessary to provide a definitive answer concerning lon