Hormone Measurements Research Articles

Maternal hypothyroidism and the risk of preeclampsia: a Danish national and regional study

BackgroundMaternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se.MethodsWe conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity.ResultsIn the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1–5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)).ConclusionsIn two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.

Pre-analytical stability and physiological fluctuations affect plasma steroid hormone outcomes: A real-world study

Since steroids are crucial for diagnosing endocrine disorders, the lack of research on factors that affect hormone levels makes interpreting the results difficult. Our study aims to assess the stability of the pre-analytical procedure and the impact of hormonal physiological fluctuations using real-world data. The datasets were created using 12,418 records from individuals whose steroid hormone measurements were taken in our laboratory between September 2019 and March 2024. 22 steroid hormones in plasma by a well-validated liquid chromatography tandem mass spectrometry method were measured. After normalization transformation, outlier removal, and z-score normalization, generalized additive models were constructed to evaluate preanalytic stability and age, sex, and sample time-dependent hormonal fluctuations. Most hormones exhibit significant variability with age, particularly steroid hormone precursors, sex hormones, and certain corticosteroids such as aldosterone. 18-hydroxycortisol, 18-oxocortisol. Sex hormones varied between males and females. Levels of certain hormones, including cortisol, cortisone, 11-deoxycortisol, 18-hydroxycortisol, 18-oxocortisol, corticosterone, aldosterone, estrone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, 11-ketotestosterone, and 11-hydroxytestosterone, fluctuated with sampling time. Moreover, levels of pregnenolone and progesterone decreased within 1 hour of sampling, with pregnenolone becoming unstable with storage time at 4 degrees after centrifugation, while other hormone levels remained relatively stable for a short period of time without or after centrifugation of the sample. This is the first instance real-world data has been used to assess the pre-analytic stability of plasma hormones and to evaluate the impact of physiological factors on steroid hormones.

A clustering approach identifies an Autism Spectrum Disorder subtype more responsive to chronic oxytocin treatment

Over the last decade, a number of clinical trials have reported effects of chronic treatment with intranasal oxytocin on autistic symptoms but with inconsistent findings. Autism is a heterogeneous disorder and one factor which may influence treatment outcome is whether a subtype of individuals is more sensitive to oxytocin. In a recent cross-over trial on 41 young autistic children we reported that 44% showed a reliable improvement in clinical symptoms (Autism Diagnostic Observation Schedule, ADOS-2) after a placebo-controlled, 6-week intranasal oxytocin intervention where treatment was given every other day followed by a period of positive social interaction. In the current re-assessment of the data, we used an unsupervised data-driven cluster analysis approach to identify autism subtypes using 23 different demographic, social subtype, endocrine, eye-tracking and clinical symptom measures taken before treatment and this revealed an optimum of two different subtypes. We then assessed the proportion of identified responders to oxytocin and found that while 61.5% of one subtype included responders only 13.3% of the other did so. During the placebo phase there was no difference between the two subtypes for the small proportion of responders (19.2% vs 6.7%). This oxytocin-sensitive subtype also showed overall significant post-treatment clinical and eye-tracking measure changes. The oxytocin-sensitive subtype was primarily characterized at baseline by lower initial clinical severity (ADOS-2) and greater interest in the eye-region of emotional faces. These features alone were nearly as efficient in identifying the two subtypes as all 23 baseline measures and this easy-to-conduct approach may help rapidly and objectively screen for oxytocin responders. Future clinical trials using oxytocin interventions may therefore achieve greater success by focusing on children with this specific autism subtype and help develop individualized oxytocin intervention.

Early postoperative growth hormone measurement as a predictive marker for acromegaly remission.

Growth hormone (GH) has a short half-life and declines abruptly following somatotropinoma surgery, enabling its prompt measurement as an indicator of surgical success. This study assesses the predictive value of early postoperative GH levels for 3-month and >1-year remission of acromegaly. We conducted a retrospective search in our database of patients who had undergone transsphenoidal surgery of GH-secreting pituitary adenoma from January 2011 to June 2022. Only the patients who underwent the first pituitary surgery and had GH measurements on the fifth postoperative day were included. The 3-month and >1-year remission of acromegaly was defined as achieving the GH nadir of <0.4 μg/L during an oral glucose tolerance test and maintaining normal insulin-like growth factor 1 levels at the initial follow-up visit 3 months after surgery and throughout at least the first year postoperation. We included 63 patients in the analysis, with a median follow-up of 51.8 (13-155) months. The 3-month remission was achieved in 42 (66.7%) patients, and >1-year remission without additional therapy in 38 (60.3%) patients. Those who achieved >1-year remission had significantly lower fifth-day postoperative GH levels (0.59 [0.09-8.92] vs. 2.63 [0.25-24.64] μg/L, p < .001). Receiver-operating characteristic analysis revealed a significant value of fifth-day postoperative GH levels regarding the prediction of 3-month (area under the curve [AUC], 0.834; p < .0001) and >1-year (AUC, 0.783; p < .0001) acromegaly remission. The GH threshold of ≤1.57 μg/L yielded a sensitivity of 90.5% and a specificity of 71.4% at 3 months and 89.5% sensitivity and 60% specificity at the >1-year remission, respectively. Notably, all patients with fifth-day postoperative GH levels ≤0.23 μg/L exhibited remission of acromegaly throughout the follow-up period. Early postoperative GH measurement could be a reliable predictor of both 3-month and >1-year remission of acromegaly.

Association between Chronic Kidney Disease-Mineral and Bone Disorder Biomarkers and Symptom Burden in Older Patients with Advanced Chronic Kidney Disease: Results from the EQUAL Study.

Patients with advanced chronic kidney disease (CKD) develop numerous symptoms, with a multifactorial origin. Evidence linking mineral disorders (CKD-MBD) and uremic symptoms is scant and mostly limited to dialysis patients. Here we aim to assess the association between CKD-MBD and symptom burden in non-dialysis CKD patients. We used data from the European Quality study, which includes patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries, followed up to five years. We used generalized linear mixed-effect models to determine the association between repeated measurements of parathyroid hormone (PTH), phosphate and calcium with the overall symptom number (0-33), the overall symptom severity (0-165), and the presence of 33 CKD-related symptoms. We also analyzed subgroups by sex, age, and diabetes mellitus, and assessed effect mediation and joint effects between mineral biomarkers. The 1396 patients included in the study had a mean of 13±6 symptoms at baseline, with a median overall severity score of 32 (IQR 19-50). The association between PTH levels and symptom burden appeared U-shaped with a lower symptom burden found for mild-to-moderately increased PTH levels. Phosphate and calcium were not independently associated with overall symptom burden. The highest symptom burden was found in patients with a combination of both severe hyperparathyroidism and severe hyperphosphatemia (+2.44 symptoms (0.50, 4.38), P=0.01). The association of both hypocalcemia and hyperphosphatemia with symptom burden seemed to differ by sex and age. In older patients with advanced CKD not on dialysis, mild-to-moderately increased PTH was associated with a lower symptom burden, although the effect size was relatively small (less than one symptom). Neither phosphate nor calcium were associated with the overall symptom burden, except for the combination of severe hyperphosphatemia and severe hyperparathyroidism which was associated with an increased number of symptoms.

The Course of Minipuberty in Daughters of Women with Low Gestational Vitamin D Status.

Minipuberty is a term describing temporary, sex-specific activation of the hypothalamic-pituitary-gonadal axis, which is implicated in the development of male and female genital organs. Sons of women with low vitamin D during gestation were found to be characterized by increased activity of the reproductive axis and faster postnatal growth of genital organs. The current study assesses for the first time the course of minipuberty in female descendants of women with a vitamin D deficit. The study population included three matched groups of infant girls: children born to women with vitamin D deficiency (25OHD concentration below 50 nmol/L), offspring of women with vitamin D insufficiency (25OHD concentration between 50 and 75 nmol/L), and daughters of healthy females (25OHD concentration between 75 and 150 nmol/L). Salivary concentrations of estradiol, progesterone, 17-hydroxyprogesterone and androgens, as well as urine concentrations of FSH and LH, were assayed during the first 18 months of life (once a month in the first 6 months, bimonthly between months 6 and 12, and then every three months). At each visit, beyond hormone measurements, the investigators assessed the size of reproductive organs: ovaries, uterus and breasts. In daughters of mothers with vitamin D deficiency, concentrations of FSH, LH and estradiol were higher and detectable for a longer period of time, while ovarian volume, uterine length and breast diameter were greater than in the remaining groups. Children born to women with vitamin D insufficiency were characterized by higher FSH levels than daughters of healthy females, though the detection period was the same, and both groups differed in breast diameter. These findings suggest that low vitamin D status during gestation leads to more pronounced and longer-lasting activation of the reproductive axis, and is associated with increased dimensions of sexual organs, the magnitude of which depends on the degree of vitamin D deficit.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. Post-hoc analyses of prospective cohort studies. Clinical research center. Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age

In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences-0.07 (95% CI -0.13,-0.02),-0.09 (-0.15,-0.02),-0.08 (95% CI -0.14,-0.02), and-0.08 (-0.13,-0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Towards Personalized TSH Reference Ranges: A Genetic and Population-Based Approach in Three Independent Cohorts.

Background: Serum thyroid-stimulating hormone (TSH) measurement is the diagnostic cornerstone for primary thyroid dysfunction. There is high inter-individual but limited intra-individual variation in TSH concentrations, largely due to genetic factors. The currently used wide population-based reference intervals may lead to inappropriate management decisions. Methods: A polygenic score (PGS) including 59 genetic variants was used to calculate genetically determined TSH reference ranges in a thyroid disease-free cohort (n = 6,834). Its effect on reclassification of diagnoses was investigated when compared to using population-based reference ranges. Next, results were validated in a second independent population-based thyroid disease-free cohort (n = 3,800). Potential clinical implications were assessed in a third independent population-based cohort including individuals without thyroid disease (n = 26,321) as well as individuals on levothyroxine (LT4) treatment (n = 1,132). Results: PGS was a much stronger predictor of individual TSH concentrations than FT4 (total variance in TSH concentrations explained 9.2-11.1% vs. 2.4-2.7%, respectively) or any other nongenetic factor (total variance in TSH concentrations explained 0.2-1.8%). Genetically determined TSH reference ranges differed significantly between PGS quartiles in all cohorts, while the differences in FT4 concentrations were absent or only minor. Up to 24.7-30.1% of individuals, previously classified as having subclinical hypo- and hyperthyroidism when using population-based TSH reference ranges, were reclassified as euthyroid when genetically determined TSH reference ranges were applied. Individuals in the higher PGS quartiles had a higher probability of being prescribed LT4 treatment compared to individuals from the lower PGS quartiles (3.3% in Q1 vs. 5.2% in Q4, Pfor trend =1.7 × 10-8). Conclusions: Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions. As the currently used PGS can only predict approximately 10% of inter-individual variation in TSH concentrations, it should be further improved when more genetic variants determining TSH concentrations are identified in future studies.

Circulating adrenal and gonadal steroid hormones heterogeneity in active young males and the contribution of 11-oxy androgens

The classical androgens, testosterone and dihydrotestosterone, together with dehydroepiandrosterone, the precusrsor to all androgens, are generally included in diagnostic steroid evaluations of androgen excess and deficiency disorders and monitored in androgen replacement and androgen suppressive therapies. The C11-oxy androgens also contribute to androgen excess disorders and are still often excluded from clinical and research-based steroids analysis. The contribution of the C11-oxy androgens to the androgen pool has not been considered in androgen deficiency. An exploratory investigation into circulating adrenal and gonadal steroid hormones in men was undertaken as neither the classical androgens nor the C11-oxy androgens have been evaluated in the context of concurrent measurement of all adrenal steroid hormones. Serum androgens, mineralocorticoids, glucocorticoids, progesterones and androgens were assessed in 70 healthy young men using ultra high performance supercritical fluid chromatography and tandem mass spectrometry. Testosterone, 24.5 nmol/L was the most prominent androgen detected in all participants while dihydrotestosterone, 1.23 nmol/L, was only detected in 25% of the participants. The 11-oxy androgens were present in most of the participants with 11-hydroxyandrostenedione, 3.37 nmol, in 98.5%, 11-ketoandrostenedione 0.764 in 77%, 11-hydroxytestosterone, 0.567 in 96% and 11-ketotestosterone: 0.440 in 63%. A third of the participants with normal testosterone and comparable 11-ketotestosterone, had significantly lower dehydroepiandrosterone (p < 0.001). In these males 11-hydroxyandrostenedione (p < 0.001), 11-ketoandrostenedione (p < 0.01) and 11-hydroxytestosterone (p < 0.006) were decreased. Glucocorticoids were also lower: cortisol (p < 0.001), corticosterone (p < 0.001), cortisone (p < 0.006) 11-dehydrocorticosterone (p < 0.001) as well as cortisol:cortisone (p < 0.001). The presence of dehydroepiandrosterone was associated with 16-hydroxyprogesterone (p < 0.001), which was also significantly lower. Adrenal and gonadal steroid analysis showed unexpected steroid heterogeneity in normal young men. Testosterone constitutes 78% of the circulating free androgens with the 11-oxy androgens abundantly present in all participants significantly contributing 22%. In addition, a subset of men were identified with low circulating dehydroepiandrosterone who showed altered adrenal steroids with decreased glucocorticoids and decreased C11-oxy androgens. Analysis of the classical and 11-oxy androgens with the additional measurement of dehydroepiandrosterone and 16-hydroxyprogesterone may allow better diagnostic accuracy in androgen excess or deficiency.

Malignant solitary fibrous tumor of the kidney with IGF2 secretion and without hypoglycemia

BackgroundSolitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal tumor that mostly involves the pleura and infrequently involves extra-pleural sites. De novo SFT of the kidney is uncommon, and malignant SFT is extremely rare.Case presentationWe report a case of a 51-year-old man with a large malignant SFT in the left kidney. Pathological examination confirmed the diagnosis of SFT based on typical morphology, nuclear STAT6 expression, and NAB2-STAT6 gene fusion. The malignant subtype was determined by a large tumor size (≥ 15 cm) and high mitotic counts (8/10 high-power fields). KRAS mutation was identified by DNA sequencing. Insulin-like growth factor 2 (IGF2) was diffusely and strongly expressed in tumor cells, however, hypoglycemia was not observed. Hyperglycemia and high adrenocorticotropic hormone (ACTH) concentration were observed one month after surgery. Hormone measurements revealed normal blood cortisol and aldosterone levels, and increased urinary free cortisol level. A pituitary microadenoma was identified using brain magnetic resonance imaging, which may be responsible for the promotion of hyperglycemia.ConclusionsWe report a case of renal malignant SFT with a KRAS mutation, which was previously unreported in SFT and may be associated with its malignant behavior. Additionally, we emphasize that malignant SFT commonly causes severe hypoglycemia due to the production of IGF2. However, this effect may be masked by the presence of other lesions that promote hyperglycemia. Therefore, when encountering a malignant SFT with diffuse and strong IGF2 expression and without hypoglycemia, other lesions promoting hyperglycemia need to be ruled out.

Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome.

Do hyperactive kisspeptin neurons contribute to abnormally high LH secretion and downstream hyperandrogenemia in polycystic ovary syndrome (PCOS)-like conditions and can inhibition of kisspeptin neurons rescue such endocrine impairments? Targeted inhibition of endogenous kisspeptin neuron activity in a mouse model of PCOS reduced the abnormally hyperactive LH pulse secretion and hyperandrogenemia to healthy control levels. PCOS is a reproductive disorder characterized by hyperandrogenemia, anovulation, and/or polycystic ovaries, along with a hallmark feature of abnormal LH hyper-pulsatility, but the mechanisms underlying the endocrine impairments remain unclear. A chronic letrozole (LET; aromatase inhibitor) mouse model recapitulates PCOS phenotypes, including polycystic ovaries, anovulation, high testosterone, and hyperactive LH pulses. LET PCOS-like females also have increased hypothalamic kisspeptin neuronal activation which may drive their hyperactive LH secretion and hyperandrogenemia, but this has not been tested. Transgenic KissCRE+/hM4Di female mice or littermates Cre- controls were treated with placebo, or chronic LET (50 µg/day) to induce a PCOS-like phenotype, followed by acute (once) or chronic (2 weeks) clozapine-N-oxide (CNO) exposure to chemogenetically inhibit kisspeptin cells (n = 6 to 10 mice/group). Key endocrine measures, including in vivo LH pulse secretion patterns and circulating testosterone levels, were assessed before and after selective kisspeptin neuron inhibition and compared between PCOS groups and healthy controls. Alterations in body weights were measured and pituitary and ovarian gene expression was determined by qRT-PCR. Acute targeted inhibition of kisspeptin neurons in PCOS mice successfully lowered the abnormally hyperactive LH pulse secretion (P < 0.05). Likewise, chronic selective suppression of kisspeptin neuron activity reversed the previously high LH and testosterone levels (P < 0.05) down to healthy control levels and rescued reproductive gene expression (P < 0. 05). N/A. Ovarian morphology was not assessed in this study. Additionally, mouse models can offer mechanistic insights into neuroendocrine processes in PCOS-like conditions but may not perfectly mirror PCOS in women. These data support the hypothesis that overactive kisspeptin neurons can drive neuroendocrine PCOS-like impairments, and this may occur in PCOS women. Our findings complement recent clinical investigations using NKB receptor antagonists to lower LH in PCOS women and suggest that pharmacological dose-dependent modulation of kisspeptin neuron activity may be a valuable future therapeutic target to clinically treat hyperandrogenism and lower elevated LH in PCOS women. This research was supported by NIH grants R01 HD111650, R01 HD090161, R01 HD100580, P50 HD012303, R01 AG078185, and NIH R24 HD102061, and a pilot project award from the British Society for Neuroendocrinology. There are no competing interests.

Methods of Determining Energy Expenditure in Individuals with Prader-Willi Syndrome: A Systematic Literature Review.

Prader-Willi syndrome (PWS) is a rare disorder characterised by varying nutritional phases that occur throughout the lifespan, ranging from failure to thrive to hyperphagia. If uncontrolled, the imbalance between energy intake and expenditure results in obesity development and increased morbidity and mortality risk. Although measures of energy requirements for accurate nutrition assessment are vital, the evidence appears sparse and heterogeneous; hence, the aim of this review was to examine the available literature on energy expenditure predicted or measured using various methods in individuals with PWS. Studies were sought that presented methods and results on resting energy expenditure or basal metabolic rate. A narrative synthesis was completed to present the study characteristics and results. Methods of determining energy requirements included predictive equations and indirect calorimetry. Differences amongst ages, growth hormone therapy, fasting status, and measures in which results were presented were limitations to appropriately summarising and identifying trends in energy expenditure. Indirect calorimetry was identified as the most accurate method; however, it is not widely available in all settings. Further research is encouraged to support the development of valid and reliable predictive equations that will better inform and improve the efficiency of clinical practice in supporting people with PWS.

Blood Sampling and Hormone Measurement for Determining the Stage in the Ovarian Cycle in Marmosets.

Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.

P-723 Egg-conomized frozen embryo transfer

Abstract Study question Is home-based monitoring of ovulation cost effective compared with hospital-controlled ovulation in women undergoing frozen embryo transfer in the natural cycle? Summary answer Home-based monitoring to time frozen-embryo-transfer is cost-effective compared to hospital-controlled ovulation, as it results in lower cost with no difference in ongoing pregnancy rates. What is known already Women undergoing frozen embryo transfer treated by home-based monitoring of ovulation or hospital-controlled ovulation have comparable ongoing pregnancy rates. We found no differences in secondary outcomes, including the risk of undetected ovulation. Complete home-based monitoring of ovulation with LH hormone kits is feasible and requires no hospital visits at lower costs since ultrasound monitoring and hCG injection are no longer needed. Both consequences imply potentially lower costs after home-based monitoring of ovulation. Study design, size, duration We performed an economic evaluation of home-based monitoring of ovulation compared with hospital-controlled ovulation in a national multicentre randomised controlled trial in women undergoing frozen embryo transfer (ANTARCTICA-2 RCT Dutch TrialRegister Trial NL6414). 1464 women were randomly assigned between April 10, 2018, and April 13, 2022, with 732 allocated to home-based monitoring and 732 to hospital-controlled monitoring. All randomized patients were included according to the intention-to-treat principle. Participants/materials, setting, methods We performed a cost-effectiveness analysis from a hospital and societal perspective. We compared the direct medical costs of home-based monitoring of ovulation and hospital-controlled ovulation during one cycle until an ongoing pregnancy occurred. Direct medical costs included digital ovulation tests, transvaginal ultrasound monitoring of the dominant follicle followed by hCG trigger, hormone measurements in blood, treatment for miscarriage or ectopic pregnancy. Nonparametric bootstrapping was used to calculate cost estimates and differences with 95% confidence intervals. Main results and the role of chance Ongoing pregnancy rates were 20·8% in the home-based monitoring group and 20·9% in the hospital-controlled group (risk ratio [RR] 0·99 [90% CI 0·81 to 1·22]; risk difference [RD] -0·14 [90% CI -3·63 to 3·36]). No differences in ectopic pregnancies or miscarriages were found. Home-based monitoring required less travelling to the hospital, less ultrasounds by doctors or nurses, less hormone measurements in blood, and less medication (hCG injections). Mean direct medical costs per woman in the home-based monitoring of ovulation group and in the hospital-controlled ovulation group were €752 versus €991, respectively, with a mean difference of €239. The ICER consistently showed home-based monitoring to be less costly with no difference in effectiveness. Consequently, the cost difference from a societal perspective was larger. The mean costs per woman in the home-based monitoring of ovulation group and in the hospital-controlled ovulation group were €787 versus €1395, respectively, with a mean difference of €607 in favour of home-based monitoring. Limitations, reasons for caution We report on one cycle per women. Women usually undergomultiple frozen-embryo-cycles. This is of importance for clinical decision making aboutimplementation of home-based monitoring, since the cumulative benefit of multiple cycles perwoman should be taken into account. Wider implications of the findings The results of our trial show that home-based monitoring time frozen embryo transfer is equally effective but less costly compared with hospital-controlled ovulation. In this era of climate change and shortages of hospital staff and waiting lists, any process that takes less human labour is important. Trial registration number Dutch Trial Register (Trial NL6414)

P-407 Exploring the effectiveness of tailoring estradiol supplementation duration to mimic the natural cycle length in artificial endometrial preparation for frozen embryo transfer cycles

Abstract Study question Is an estrogen supplementation duration similar in length to the follicular phase of a natural cycle associated with a better clinical pregnancy rate? Summary answer An estradiol supplementation duration, which is proportional to the natural follicular phase length, results in significantly better outcomes compared to shorter exposure durations What is known already The last decade witnessed a major increase in the use of single euploid frozen embryos. Artificial endometrial preparation (AEP) has proven to be effective to prepare the endometrium for implantation. However, several features of AEP need to be clarified mainly the duration of estrogen supplementation and until now no study took into consideration the difference between exogenous estrogen supplementation and the actual length of the follicular phase of each patient during AEP. Furthermore, most of the studies focused on upper limit of estrogen exposure while few considered the lower limit. Unfortunately, the results on pregnancy rates were mixed. Study design, size, duration 663 single euploid frozen embryo transfer cycles were included. Patients underwent vaginal ultrasound and hormonal blood measurement (Estradiol, Progesterone) on day 2 of their cycle. Estradiol valerate (4 mg the first 2 days then 6 mg daily, Orally) was started on the same day and another control was done around day 10. When triple lining pattern of the endometrium was seen, vaginal progesterone was initiated (800 mg daily) and SET was done after 120 hours. Participants/materials, setting, methods Patients with reported regular menstrual cycle (25-35 days) were included and the difference between estrogen supplementation and the actual follicular phase was calculated for each patient. Patients were sorted into 2 groups as follows: 231 women with normal interval (±2 days of follicular phase length), and 432 women with short interval (-3 days or shorter). Only the first single euploid embryo transfer cycles were analyzed for these patients. Main results and the role of chance Whereas patients had similar characteristics in both groups, the corresponding clinical pregnancy rates in normal and short supplementation groups were 69.3% (160/231) and 64% (277/432), respectively. After balancing the groups for BMI, embryo quality and endometrial thickness with inverse treatment probability weighting, those who received estradiol supplementation proportional to their natural follicular phase length had significantly higher clinical pregnancy rates compared to those who received it for shorter durations (adjusted OR: 1.48, 95% CI: 1.16 – 1.89, P = 0.002). Serum estradiol levels were available for 523 cycles, the clinical pregnancy rate in those within the 1st quartile (&amp;lt;155pmol/L), 2nd to 3rd quartile (155 to 275pmol/L) and 4th quartile (&amp;gt;275pmol/L) were 70%, 64.7% and 63%. After adjusting for BMI and embryo quality, higher (&amp;gt;275pmol/L) (adjusted OR: 0.84, 95% CI: 0.53-1.32, P = 0.442) and lower(&amp;lt;155pmol/L) (adjusted OR: 1.37, 95% CI: 0.85-2.22, P = 0.202) estradiol levels were not significantly associated with clinical pregnancy. Limitations, reasons for caution The present study could not address the influence of very long estrogen supplementation on clinical pregnancy rate due to limited samples. Further prospective studies, including larger populations, are needed to confirm our findings Wider implications of the findings Our data indicate that mimicking individually the natural cycle regarding estrogen supplementation duration in AEP for single euploid embryo transfer cycles can produce significant improvement in clinical pregnancy rates. Trial registration number not applicable

Overview of prevalence, etiology, clinical features, diagnosis, and management of primary ovarian insufficiency

Primary ovarian insufficiency (POI) is the development of primary hypogonadism before the age of 40 years in women with normal karyotypes. Patients present with symptoms that are similar to those of menopause, including irregular periods, reduced fertility, and climacteric symptoms due to hypoestrogenism, such as hot flashes, vaginal dryness, dyspareunia, irritability, and night sweats. The incidence of spontaneous POI is approximately 1 in 250 by 35 years of age and 1 in 100 by 40 years of age. Genetic, inflammatory, metabolic, autoimmune, and idiopathic factors contribute to POI. POI pathophysiology is explained by the presence of fewer primordial follicles and their rapid degeneration. Detailed history and examination are important for diagnosis. Diagnosis requires biochemical evidence and laboratory testing, including measurements of follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, and estradiol (E2) levels. In addition, transvaginal ultrasound is preferred to evaluate ovarian reserve. POI should be managed through a multidisciplinary approach involving gynecologists, endocrinologists, and psychologists. Hormonal replacement therapy is the mainstay treatment for all women with POI. Lifestyle modifications such as weight-bearing exercises, smoking cessation, and Vitamin D and calcium supplementation are highly recommended to improve bone density and reduce fractures. Psychological care has been suggested to improve self-esteem and social support, along with family planning guidance. Despite recent discoveries, additional screening techniques are needed.

The role of mesenchymal stem cell therapy in ameliorating diabetes-induced ovarian damage in albino rats: Histological, biochemical and immunohistochemical studies

Background Diabetes mellitus (DM) is a chronic disease causing a variety of complications that can damage most organs, including the gonads. Diabetes was reported to be effectively treated using mesenchymal stem cells (MSCs). Objective The objective of the work was to demonstrate the therapeutic role of stem cells in cases of ovarian damage due to diabetes. Materials and methods Eighteen adult female albino rats were divided evenly into three groups. The control group received an injection of 1 ml of saline intraperitoneally (i.p.). The streptozotocin (STZ)-treated group: that was given 60 mg/kg per body weight (i.p.) of STZ to induce DM, which was slaughtered after 4 weeks. The STZ+stem cell-treated group that got STZ then was allowed to recover for 4 weeks and then underwent an intravenous injection of one million MSC before being sacrificed. Measurements of blood glucose, serum estradiol (E2), follicular-stimulating hormone (FSH), and luteinizing hormone (LH) were performed. Histological examination with hematoxylin and eosin, Masson stain, and immunohistochemical investigation for proliferating cell nuclear antigen (PCNA) were performed on the ovarian sections. Results and conclusion The STZ-induced DM group showed high glucose, FSH, and LH levels and decreased the E2 levels. Also, the inflammation, degeneration, and decreased PCNA immune expression of the ovary development in the STZ-induced DM group were observed. The treatment with the MScs reversed the effect of DM on glucose, FSH, LH, and E2. Additionally, the MScs improved the pathological alterations by increasing PCNA immune expression in the ovary. It was concluded that MSCs can effectively treat diabetes-induced ovarian damage.

Diagnosis of Pregnancy in Iraqi Awassi Ewes Through Progesterone Hormone Measurement and Ultrasonography Following Induction of Fertile Estrus with Sulpiride

Diagnosis of Pregnancy in Iraqi Awassi Ewes Through Progesterone Hormone Measurement and Ultrasonography Following Induction of Fertile Estrus with Sulpiride

A Randomized, Crossover Trial Assessing Appetite, Energy Metabolism, Blood Biomarkers, and Ad Libitum Food Intake Responses to a Mid-Morning Pecan Snack vs. an Equicaloric High-Carbohydrate Snack in Healthy Volunteers with Overweight/Obesity.

The differential effects of pecans versus other popular snack foods on appetite and blood markers of metabolism and satiety have not been well studied. This study investigated the effects of a single mid-morning snack of pecans or tortilla chips on subjective appetite, food intake, blood measures of hormones and metabolites, and resting energy expenditure. Twenty participants with overweight and obesity were enrolled in a within-participants, randomized crossover trial. Participants had indwelling catheters placed for blood sampling and were fed a standardized breakfast, followed two hours later by a 250 kcal snack of either pecans or tortilla chips, and then by a self-selected lunch. Visual analog scale (VAS) appetite measures, blood markers, and energy expenditure were taken at intervals after food consumption. VAS ratings, energy, food intake and macronutrient composition did not differ between treatment conditions, but glucose and insulin were significantly more elevated after tortilla chips. Free fatty acids (FFA), triglycerides (TG), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were higher after consuming pecans compared to tortilla chips. Pecan consumption improves postprandial glucose and insulin profiles which would be beneficial to individuals at risk of developing type 2 diabetes. Further studies are needed to investigate whether increased relative secretion of PYY and GLP-1 after eating pecans versus tortilla chips may affect subjective appetite and energy intake if consumed chronically.