Soluble luteinizing hormone receptor in follicular fluid and the association with reproductive function during IVF and ICSI.

The need for assisted reproductive technology (ART) has increased worldwide, leaving a negative impact on both physical and emotional health of the individual as well as on society depending on child births, thus biomarkers that can increase the success of ART are warranted. The luteinizing hormone/choriogonadotropin receptor (LHCGR) is released into blood and follicular fluid, and the level of soluble LHCGR (sLHCGR) in serum has previously been suggested to predict chances of pregnancy and live birth rate after ART. We aimed to investigate whether sLHCGR originates from the ovary and if serum or follicular fluid sLHCGR can predict the likelihood of pregnancy or live birth.

Influence of cholecalciferol supplementation on changes in total 25OHD, free 25OHD, and free 25OHD % in relation to calcium, bone, and glucose homeostasis in young, infertile men.

Background And Objective: While all types of vitamin D metabolites are bound to vitamin D binding protein and albumin leaving only a small fraction in its free active form, only serum concentrations of total 25-hydroxy vitamin D (25OHD) are used to determine vitamin D status in clinical practice. This study aimed to describe the association of total 25-hydroxy vitamin D (25OHD), calculated free 25OHD, and free 25OHD% (free 25OHD × 100 %/total 25OHD) with mineral, bone, and metabolic variables and assess the impact of cholecalciferol supplementation.

Research Design And Methods: Secondary data from a single-center, double-blinded, randomized, placebo-controlled clinical trial (NCT01304927) in 307 infertile men.

Weight Loss Induces Changes in Vitamin D Status in Women with Obesity but not in Men: a Randomized Clinical Trial.

Context: Obesity is associated with low vitamin D and recent studies have suggested a difference in vitamin D metabolism between females and males.

Objective: The aim of this study was to investigate the effects of weight loss on vitamin D status in individuals with obesity, and secondarily, whether vitamin D metabolism differs between women and men.

Methods: Secondary analysis from a randomized placebo-controlled trial, designed to investigate the efficacy of 52 weeks of treatment with either liraglutide, exercise or combined, compared with placebo on weight loss maintenance after an 8-week low-calorie diet-induced weight loss in 195 individuals with obesity (BMI 32-43 kg/m2).

Heterogenous Origins of Calcium Homeostasis Disorders Arising from Five Heterozygous Calcium-Sensing Receptor Variants.

Context And Objectives: The human calcium-sensing receptor (CaSR) plays a key role in calcium homeostasis, and most identified CASR variants are associated with hypercalcemic and hypocalcemic disorders. Here we characterized the pharmacological implications of five heterozygous CASR variants from individuals with familial hypocalciuric hypercalcemia 1 [FHH1: Y63C, I81T, Q459R, W818stop] or autosomal dominant hypocalcemia 1 [ADH1: R955stop].

Methods: Total and cell surface expression levels of wild-type (WT) and variant CaSRs expressed in human embryonic kidney 293T (HEK293T) cells were determined using ELISA, and the pharmacological properties of the receptors were delineated in two functional assays.

Novel approach for oligospermia (NAPO) - Protocol for a randomized controlled trial.

Background: Infertility affects millions of couples globally, with up to 40-50 % of cases linked to impaired semen quality. Insemination or in vitro fertilization are used frequently, regardless of the cause of infertility due to the lack of specific medical interventions for male infertility. Denosumab, an antibody blocking RANKL signaling, may enhance semen quality in infertile men.

Debulking surgery after muscular paraffin oil injections: Effects on calcium homeostasis and patient satisfaction.

Objective: Cosmetic paraffin oil injections can lead to granuloma formation causing hypercalcemia and kidney failure. This study explores whether debulking surgery is an effective treatment for improving calcium homeostasis, inflammation and clinical symptoms.

Materials And Methods: In a retrospective study, we reviewed 33 patients undergoing debulking surgery.

Loss-of-Function Thr347Ala Variant in the G Protein Subunit-α11 Causes Familial Hypocalciuric Hypercalcemia 2 (FHH2).

Context And Objectives: To date, only four loss-of-function variants in the GNA11 gene encoding the G protein subunit α11 (Gα11) leading to familial hypocalciuric hypercalcemia 2 (FHH2) have been characterized. Gα11 is involved in calcium-sensing receptor (CaSR) signaling, and loss-of-function variants in GNA11 lead to reduced agonist potency at CaSR and an FHH phenotype.

Design And Participants: We have identified a family with a heterozygous GNA11 Thr347Ala variant and characterized its impact on calcium homeostasis in FHH2 patients and the signaling properties of CaSR through the Gα11-Thr347Ala variant in vitro.

Injection of luteinizing hormone or human chorionic gonadotropin increases calcium excretion and serum PTH in males.

Animal and human studies have suggested that sex steroids have calciotropic actions, and it has been proposed that follicle-stimulating hormone (FSH) may exert direct effects on bone. Here, we demonstrate the expression of the receptor for Luteinizing hormone (LH) and human choriogonadotropin (hCG), LHCGR, in human kidney tissue, suggesting a potential influence on calcium homeostasis. To investigate the role of LHCGR agonist on calcium homeostasis in vivo, we conducted studies in male mice and human subjects.

Low-serum antimüllerian hormone is linked with poor semen quality in infertile men screened for participation in a randomized controlled trial.

Objective: To investigate possible associations between serum antimüllerian hormone (AMH) concentration and semen quality in infertile men. Studies investigating the associations between serum AMH concentration and semen quality in infertile men have shown conflicting results.

Design: Infertile men were included during screening for participation in the First in Treating Male Infertility Study, a double-blinded, placebo-controlled, 1:1, single-center randomized controlled trial.

Case report: Death caused by multi-organ metastatic calcifications as a result of intramuscular injections with paraffin oil.

In this forensic case report, we present autopsy findings from a young male in his thirties who had been self-injecting paraffin oil into his upper extremities 8 years prior to death. The injections induced an inflammatory response, leading to granuloma formation. This, in turn, resulted in severe hypercalcemia.

High-dose vitamin D supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections.

Background: Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs.

Ovarian follicular fluid levels of phthalates and benzophenones in relation to fertility outcomes.

Background: Many endocrine disrupting chemicals (EDCs), for instance phthalates and benzophenones, are associated with adverse fertility outcomes and semen quality parameters.

Objective: To evaluate if concentrations of selected phthalate metabolites and benzophenones measured in follicular fluid are associated with fertility outcomes (i.e.

Calcium and vitamin D homoeostasis in male fertility.

Calcium and vitamin D have well-established roles in maintaining calcium balance and bone health. Decades of research in human subjects and animals have revealed that calcium and vitamin D also have effects on many other organs including male reproductive organs. The presence of calcium-sensing receptor, vitamin D receptor, vitamin D activating and inactivating enzymes and calcium channels in the testes, male reproductive tract and human spermatozoa suggests that vitamin D and calcium may modify male reproductive function.

High-dose cholecalciferol supplementation to obese infertile men is sufficient to reach adequate vitamin D status.

Obesity is associated with low vitamin D status, and the optimal supplement and dosage of cholecalciferol (vitamin D) or calcidiol (25OHD) for individuals with obesity have been debated. We aimed to determine the effect of high-dose vitamin D supplementation on achieving adequate vitamin D levels among infertile men with normal weight . obesity.

Effects of vitamin D on sex steroids, luteinizing hormone, and testosterone to luteinizing hormone ratio in 307 infertile men.

Objective: Vitamin D status has been associated with sex steroid production. The question is whether vitamin D supplementation has an impact on sex steroid production in infertile men with vitamin D insufficiency?

Design: A single-center, double-blinded, randomized clinical trial. Differences in sex steroids and reproductive hormones were predefined secondary outcomes, vitamin D status at baseline was a predefined subgroup and the primary outcome was differences in semen quality.

Low serum anti-Müllerian hormone is associated with semen quality in infertile men and not influenced by vitamin D supplementation.

Background: Anti-Müllerian hormone (AMH) is released by testicular Sertoli cells and of great importance during fetal male sexual development, but less is known about the role of circulating AMH during adulthood. In vitro studies have shown that vitamin D may induce AMH transcription, but a controlled trial investigating the possible effect of vitamin D on serum AMH has not been conducted in men.

Methods: A single-center, double-blinded, randomized placebo-controlled clinical trial (NCT01304927) conducted in Copenhagen, Denmark.

Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice.

The adhesion receptor ADGRA3 (GPR125) is a known spermatogonial stem cell marker, but its impact on male reproduction and fertility has not been examined. Using a mouse model lacking Adgra3 (Adgra3 ), we show that 55% of the male mice are infertile from puberty despite having normal spermatogenesis and epididymal sperm count. Instead, male mice lacking Adgra3 exhibited decreased estrogen receptor alpha expression and transient dilation of the epididymis.

Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial.

Background: Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study.

RANKL regulates testicular cancer growth and Denosumab treatment has suppressive effects on GCNIS and advanced seminoma.

Background: Testicular germ cell tumours (TGCTs) have a high sensitivity to chemotherapy and a high cure rate, although with serious adverse effects. In the search for tumour suppressive drugs, the RANKL inhibitor Denosumab, used to treat osteoporosis, came up as a candidate since RANKL signalling was recently identified in the testis.

Methods: Expression of RANKL, RANK and OPG, and the effects of RANKL inhibition were investigated in human TGCTs, TGCT-derived cell-lines, and TGCT-xenograft models.

Treatment options for hypercalcemia after cosmetic oil injections: Lessons from human tissue cultures and a pilot intervention study.

Objective: Granuloma formation following self-administered cosmetic oil injections can lead to severe hypercalcemia and renal calcifications due to extra-renal vitamin D activation. This translational study aims to identify Prednisolone sparing therapeutics for hypercalcemia after development of granulomatous disease secondary to paraffin oil injections.

Materials And Methods: Granuloma tissue isolated from five men were cultured ex vivo and treated with selected drugs to block generation of activated vitamin D (1,25(OH)D).

Prediabetes Defined by First Measured HbA Predicts Higher Cardiovascular Risk Compared With HbA in the Diabetes Range: A Cohort Study of Nationwide Registries.

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA.

Research Design And Methods: Through registry databases, we identified 326,305 Danish patients with a first HbA between 40 and 51 mmol/mol (5.8-6.