Basal Hormone Research Articles

Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis.

Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes. PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale. Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I2 = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I2 = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I2 = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate. Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.

The Case | A 38-year-old man with hydronephrosis

A 38-year-old man was referred to the department of nephrology for the evaluation of bilateral hydronephrosis. The patient had a history of polyuria since childhood for which he had been using a desmopressin nasal spray for >20 years without a clear diagnosis. On physical examination, he had no costovertebral angle tenderness or peripheral edema. The family history revealed that his grandmother, father, aunt, uncle, and sister had similar manifestations. His laboratory findings included a serum sodium level of 140 mmol/l, a urine osmolality of 454 mOsm/kg, a serum creatinine level of 1.52 mg/dl, and basal pituitary hormone levels within the normal range.

Early hormonal recovery following endoscopic transsphenoidal surgery for silent non-functioning pituitary adenomas with hormone dysfunction

The role of transsphenoidal surgery in the recovery of preexisting hormone dysfunction from pituitary tumors remains controversial. This study aimed to investigate the incidence of hormone dysfunction among asymptomatic non-functioning pituitary adenomas and their recovery following endoscopic transsphenoidal surgery. Eligibility criteria included age under 80 years, presence of a non-functioning pituitary adenoma compressing the normal gland resulting in deviation of the stalk, absence of visual symptoms, and availability for regular follow-up using MRI and pre- and post-operative endocrinological assessments. 182 patients with silent non-functioning pituitary adenomas were included in this study between March 2014 and December 2018. All patients underwent endoscopic transsphenoidal surgery and complete hormonal evaluation, with basal hormone assays and a combined pituitary function test before and after surgery until the end of last follow-up. Preoperative assessment of hormonal function revealed that 124 of 182 patients (68.1%) had at least a single hormone dysfunction preoperatively. Among these, 61 of 124 (49.2%) had a dysfunction in a single axis, and 63 (50.8%) had a hormone dysfunction in two or more axes. Overall, the median endocrinological follow-up duration was 15.0 months (6-57 months). At 1 month following surgery, 91 patients (73.4%) with hormone dysfunction experienced improvement in at least a single hormone axis. Prolactin was the most common hormone among those that recovered at the last follow up (92.8% improvement) followed by growth hormone (GH, 50.0%), thyroid stimulating hormone (TSH, 50.0%), gonadotropin (Gn, 46.9%), and adrenocorticotropic hormone (ACTH, 45.0%). Time to recovery varied from 1.1 months (for prolactin) to 2.2 months (for gonadotropin, and ACTH). In patients with preoperative deficiency in GH, and ACTH, postoperative transient diabetes insipidus was associated with poor recovery (GH: HR = 0.50, p = 0.048; ACTH: HR = 0.39, p = 0.023). Non-functioning pituitary adenomas with silent hormone dysfunction are often overlooked by clinicians and patients. We suggest that even silent hormone dysfunction in patients with non-functioning pituitary adenomas can be improved with effective surgical decompression and these tumors may be potential indications of endoscopic transsphenoidal surgery.

Homeopathic Approach in the Case of Secondary Infertility and Anosmia

A 38-year-old female patient diagnosed as secondary infertility, anosmia, myoma uteri, Hashimoto thyroiditis with the history of many unsuccessful IVF attempts regained her ability of smell, her thyroid antibody levels normalised, her basal hormones, AMH levels, ovarian follicular development and ovulation improved after 6 months of treatment with homeopathy and nutritional supports. In this case report, it is observed that many gynecological problems accompanied with infertility, anosmia and autoimmune problems like Hashimoto’s thyroiditis can be improved with a holistic approach to individual supportive therapies and homeopathy. It is hoped that this case report can be a reference for future studies in this field.

Novel nomogram-based integrated gonadotropin therapy individualization in in vitro fertilization/intracytoplasmic sperm injection: A modeling approach.

ObjectiveThis study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose.MethodsThis observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-Emax, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group.ResultsThe Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women’s age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use.ConclusionBased on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

Supraphysiological estradiol levels on the hCG trigger day are associated with SGA for singletons born from fresh embryo transfer.

The effects of supraphysiological estradiol (E2) on neonatal outcomes and the significance of specific E2 concentrations remain unclear. The purpose of this study was to investigate whether supraphysiological E2 levels on the human chorionic gonadotropin (hCG) trigger day are associated with small size for gestational age (SGA) in singletons born from fresh embryo transfer (ET) cycles. Patients with singleton pregnancies who delivered after the transfer of fresh embryos, during the period from July 2012 to December 2017, at our center were included. We excluded cycles involving a vanishing twin, maternal age >35 years, basal follicle-stimulating hormone ≥10 mIU/ml, or anti-Müllerian hormone ≤1 ng/ml. We then divided all cycles into five groups by E2 level on trigger day: group A, <2000 pg/ml (reference group); group B, 2000 pg/ml≤E2<2999 pg/ml; group C, 3000 pg/ml≤E2<3999 pg/ml; group D, 4000 pg/ml≤E2<4999 pg/ml; and group E, ≥5000 pg/ml. The prevalence of SGA among singletons from fresh ET was the primary outcome. The SGA rate significantly increased when the E2 level was ≥4000 pg/ml, as observed by comparing groups D (odds ratio [OR]: 1·79, 95% confidence interval [CI]: 1·16-2·76, P = 0·01) and E (OR: 1·68, 95% CI: 1·10-2·56, P = 0·02) with the reference group. Multivariate logistic regression indicated that a serum E2 level of at least 4000 pg/ml on the hCG trigger day was associated with increased SGA and with significant differences for groups D (adjusted OR [AOR]: 1·65, 95% CI: 1·05-2·59, P = 0·03) and E (AOR: 1·60, 95% CI: 1·03-2·53, P = 0·04) relative to the reference group. In conclusion, in fresh ET cycles, the supraphysiological E2 ≥4000 pg/ml on the hCG trigger day increases the risk of SGA.

Distinct Calcium Signaling for Wildtype, Loss-of-Function and Gain-of-Function Human MC4R Variants

There is compelling evidence for human melanocortin-4-receptor (hMC4R) playing a critical function regulating energy balance; yet signal transduction pathways contributing to this are unclear. The hMC4R activates multiple signaling pathways, including induced increases in cAMP and mobilization of intracellular calcium ([Ca2+]i). Recent evidence showed cAMP signaling was not a good predictor for hMC4R variant-associated obesity. We hypothesize that hMC4R mobilization of [Ca2+]i plays an important role in regulating energy balance. To test this, we developed a robust high-throughput Fura-2 ratiometric fluorescent assay to quantitatively measure [Ca2+]i in vitro. We compared basal and α-melanocyte stimulating hormone (α-MSH) activation of [Ca2+]i for hMC4R-wildtype (WT) and hMC4R-variants stably expressed in HEK293 cells. The loss-of-function variants studied were two obesity-associated variants (R7H and R18L) known to exhibit cAMP signaling similar to WT, two obesity-associated variants (H76R and L250Q) known to exhibit cAMP-constitutive activity (CA) compared to WT, and one overweight-associated variant (H158R) known to exhibit cAMP-CA compared to WT. The gain-of-function variants (V103I and I251L) studied are known to exhibit cAMP signaling similar to WT. The data for basal [Ca2+]i were pooled from three independent experiments performed with WT and all variants in each assay. Data (mean ± SEM) were analyzed using one-way ANOVA with Dunnett’s multiple comparisons. The data (mean ± SEM) for α-MSH activation of hMC4R were pooled from three independent experiments and analyzed using non-parametric sum of squares F-test for maximum best-fit values and EC50. The α-MSH activated assays were performed with each hMC4R variant alongside WT. WT hMC4R and non-CA loss-of-function variants exhibited similar basal and α-MSH activated [Ca2+]i (WT: EC50 = 1.44 nM; R7H: EC50 = 1.40 nM; R18L: EC50 = 1.12 nM). The CA loss-of-function variants exhibited significantly (p < 0.0001) increased basal [Ca2+]i compared with WT (WT = 97.6 ± 0.9 nM; H76R = 114.2 ± 1.7 nM; L250Q = 112.1 ± 2.6 nM; H158R = 110.7 ± 1.8 nM) and significantly lower EC50’s compared with WT (H76R: EC50 = 0.07 nM; p = 0.0019; L250Q: EC50 = 0.09 nM; p = 0.0066; H158R: EC50 = 0.14 nM; p = 0.0009). The gain-of-function hMC4R variants exhibited significantly (p < 0.0001) decreased basal [Ca2+]i compared with WT (WT = 97.6 ± 0.9 nM; V103I: = 86.4 ± 0.9 nM; I251L = 87.5 ± 1.0 nM) and significantly (p = 0.0001) increased α-MSH stimulated maximum [Ca2+]i compared with WT (WT = 224.5 ± 13.6 nM; V103I = 288.2 ± 31.5 nM; I251L = 295.6 ± 20.0 nM). To summarize, we show three distinct patterns of hMC4R-associated calcium signaling; (1) WT and non-CA loss-of-function, (2) CA loss-of-function and (3) non-CA gain-of-function. Future studies are required to understand how hMC4R mobilization of [Ca2+]i might contribute to the regulation of energy balance.

Maternal and Neonatal Complications in Patients With Diminished Ovarian Reserve in In-Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

BackgroundDiminished ovarian reserve (DOR) is one of the most intractable clinical issues in human reproduction and is reported to be associated with raised risk of recurrent pregnancy loss and aneuploid blastocysts. In this study, we aimed to explore whether DOR was also associated with maternal and neonatal complications in in-vitro fertilization/intracytoplasmic sperm injection cycles.MethodsA retrospective cohort study including women below 40 years of age who achieved singleton live birth after fresh embryo transfer in in-vitro fertilization/intracytoplasmic sperm injection cycles in a single center from January 2012 to June 2019 was conducted. Participants with DOR, defined as basal follicle-stimulating hormone (FSH) ≥ 10IU/L and antimullerian hormone (AMH) < 1.2ng/ml, were enrolled as the study group. The controls were 1:2 matched by age and body mass index with FSH < 10IU/L and AMH ≥ 1.2ng/ml. Maternal and neonatal complications were compared between the DOR group and the controls.ResultsA total of 579 women, 193 in the DOR group and 386 matched as controls, were included in this study. Compared to controls, the incidence of hypertensive disorders of pregnancy was significantly increased in the DOR group (5.7% vs. 2.1%, P = 0.021). DOR patients also presented slightly higher incidences of preterm birth (10.9% vs. 7.5%, P = 0.174) and low birthweight (6.2% vs. 5.4%, P = 0.704) yet without statistical significances. The incidences of gestational diabetes mellitus and placenta previa were comparable between the two groups.ConclusionCompared to women with normal ovarian reserve, women with diminished ovarian reserve might have elevated incidence of hypertensive disorders of pregnancy. Patients with diminished ovarian reserve might need more strict antenatal care.

Clinical risk score for central precocious puberty among girls with precocious pubertal development: a cross sectional study

BackgroundThe gold standard for the diagnosis of central precocious puberty (CPP) is gonadotropin-releasing hormone (GnRH) or GnRH analogs (GnRHa) stimulation test. But the stimulation test is time-consuming and costly. Our objective was to develop a risk score model readily adoptable by clinicians and patients.MethodsA cross-sectional study based on the electronic medical record system was conducted in the Children’s Hospital, Fudan University, Shanghai, China from January 2010 to August 2016. Patients with precocious puberty were randomly split into the training (n = 314) and validation (n = 313) sample. In the training sample, variables associated with CPP (P < 0.2) in univariate analyses were introduced in a multivariable logistic regression model. Prediction model was selected using a forward stepwise analysis. A risk score model was built with the scaled coefficients of the model and tested in the validation sample.ResultsCPP was diagnosed in 54.8% (172/314) and 55.0% (172/313) of patients in the training and validation sample, respectively. The CPP risk score model included age at the onset of puberty, basal luteinizing hormone (LH) concentration, largest ovarian volume, and uterine volume. The C-index was 0.85 (95% CI: 0.81–0.89) and 0.86 (95% CI: 0.82–0.90) in the training and the validation sample, respectively. Two cut-off points were selected to delimitate a low- (< 10 points), median- (10–19 points), and high-risk (≥ 20 points) group.ConclusionsA risk score model for the risk of CPP had a moderate predictive performance, which offers the advantage of helping evaluate the requirement for further diagnostic tests (GnRH or GnRHa stimulation test).

Effect of hysteroscopic septum resection on subsequent in vitro fertilization–intracytoplasmic sperm injection outcomes in cases of primary infertility

ObjectiveWomen with septate uteri are at risk for subfertility, recurrent miscarriage, and preterm birth. It is not clear if hysteroscopic septum resection is beneficial to subsequent in vitro fertilization–intracytoplasmic sperm injection o (IVF/ICSI) outcomes in women with primary infertility. Study DesignWe analyzed all 278 women with uterine septum and primary infertility between January 2011 and January 2019. In this retrospective cohort study, the patients were divided into a surgery group and an expectant (non-surgery) group. ResultsAmong them, 87 had a complete and 191 a partial septate uterus. The IVF-ET characteristics of the two groups showed no significant differences in the patients’ age, body mass index, or basal follicle-stimulating hormone, luteinizing hormone, and estradiol levels (P>0.05). The miscarriage rate in those who underwent hysteroscopic septum resection, however, was significantly reduced (5.1% vs. 12.9%, P = 0.035). In contrast, the live birth rate between the two groups revealed no significant difference (51.4% vs. 43.6%, P = 0.1771), nor did the obstetric and neonatal outcomes (P>0.05). ConclusionsHysteroscopic septum resection can be recommended prior to IVF/ICSI.

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.

Higher chromosomal aberration frequency in products of conception from women older than 32 years old with diminished ovarian reserve undergoing IVF/ICSI.

Infertile women with diminished ovarian reserve (DOR) confront an increased miscarriage rate in assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effects of DOR and female age on the molecular karyotype of products of conception (POCs) remain unknown. We analyzed POCs using a single nucleotide polymorphism (SNP) microarray from women with DOR who experienced first-trimester miscarriage in IVF/ICSI cycles. The SNP microarray revealed chromosomal abnormalities in 74.6% (47/63) of POCs, including trisomy in 83.0% (39/47). Chromosomal aberrations were more frequent in women older than 32 years old with DOR than in young women aged 20–32 years old (86.7% vs. 44.4%, P = 0.001). Univariate and multivariable analyses identified advanced age as a risk factor for chromosomal aberration-related miscarriage in women with DOR, with odds ratios of 8.125 (95% CI: 2.291–28.820, P = 0.001) and 5.867 (95% CI: 1.395–24.673, P = 0.016), respectively. The results showed that older women (older than 32 years old) with DOR had a high risk of miscarrying a chromosomally aberrant embryo/fetus, regardless of basal follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC) and previous reproductive history. This finding indicates a novel cut-off value of age for women with DOR related to chromosomal aberration-related miscarriage.

Optimal Oocyte Number in Controlled Ovarian Stimulation with Gonadotropin-Releasing Hormone Agonist/Antagonist and Day 3 Fresh Embryo Transfer.

We aimed to investigate the optimal number of oocytes retrieved in normal responders with the gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) protocol in comparison with the GnRH agonist (GnRHa) long protocol. This retrospective study is based on a single-center cohort including 657 fresh cycles with day 3 embryo transfer using the GnRHa long protocol and the GnRHant flexible protocol at the fertility clinic of a university hospital between 2005 and 2019. The rate ratios (RR) of clinical pregnancy were evaluated using log-binomial regression depending on the categories by the number of retrieved oocytes and pituitary suppression methods. After controlling for age, body mass index, and basal follicle-stimulating hormone, women with 10-11 oocytes retrieved demonstrated a significantly higher chance of clinical pregnancy compared to the reference group (4-5 oocytes) (RR 1.68, 95% CI 1.12-2.53). However, retrieval of more than 11 oocytes did not show a significant difference inpregnancy rates (PR)from the reference group. In women treated with GnRHant, a significantly higher clinical PR was also observed in women with 10-11 oocytes retrieved compared to the reference group (RR 1.90, 95% CI 1.05-3.42). In women treated with GnRHa long protocol, a higher probability of clinical pregnancy was observed (RR 1.30, 95% CI 0.98-1.73) in the group with 8-11 oocytes retrieved and it demonstrated borderline statistical significance (P = 0.07). In summary, the optimal number of oocytes for maximizing the rate of a clinical pregnancy is different according to the method of pituitary suppression. Too many oocytes do not seem to be beneficial for achieving better clinical outcomes.

A novel stop-loss DAX1 variant affecting its protein-interaction with SF1 precedes the adrenal hypoplasia congenital with rare spontaneous precocious puberty and elevated hypothalamic-pituitary-gonadal/adrenal axis responses

The case study unveils the likely mechanism of a novel stop-loss DAX1 variant preceding the prolonged precocious puberty in the adrenal hypoplasia congenital (AHC) boy.A boy aged five years and nine months initially examined for the primary adrenal insufficiency symptoms. Next-generation sequencing confirmed the X-linked inheritance of a novel stop-loss DAX1 variant: c.1411T>C/p.Ter471Gln associated with AHC in the patient. The patient was subjected to a brief clinical follow-up from 11 to 15.1 years of age. The effect of the mutant-DAX1 variant (p.Ter471Gln) on DAX1-steroidogenic factor 1 (SF1) (protein-protein) interaction was studied by protein-protein docking using the ClusPro-online tool.At 5.9 yrs of age, the patient exhibited precocious puberty with the secondary sexual characteristics of Tanner 2 stage (of 9–14 yrs of age). The patient showed primary adrenal insufficiency with diminished cortisol concentrations at blood serum (25 ng/ml) and urine (3.55 μg/24 h) levels. Upon steroidal exposure, the patient showed normalized serum cortisol levels of 45–61 ng/ml. However, the precocious puberty got prolonged with the increased penis length of 8.5 cm and the bone age of 18 yrs old during the follow-up. The patient showed increased basal serum adrenocorticotropic hormone (110->2000 pg/ml) and follicle-stimulating hormone (18.4–22.3 mIU/ml) concentrations. Following an elevated hypothalamic-pituitary-gonadal axis activity witnessed upon gonarellin stimulation. Protein-protein docking confirmed a weaker interaction between the mutant-DAX1 (p.Ter471Gln) protein and the wild-SF1 protein.Overall, we hypothesize the weakened mutant-DAX1-SF1 (protein-protein) interaction could govern the prolonged precocious puberty augmented with the elevated hypothalamic-pituitary-gonadal/adrenal axis responses via SF1-induced neuronal nitric oxide synthetase activation in the patient.

Pergolide dosing compliance and factors affecting the laboratory control of equine pituitary pars intermedia dysfunction.

Equine pituitary pars intermedia dysfunction (PPID) is treated with daily pergolide therapy. Owner compliance and its effect on PPID control have not been previously investigated. Clinical records were searched to identify the sample of animals with PPID treated with pergolide from 2016 to 2019. The signalment was noted and the dose of pergolide received calculated. Animals were classified as compliant (receiving ≥90% of the veterinarian recommended dose of pergolide) or non-compliant, and as controlled (follow-up basal adrenocorticotrophic hormone concentrations within the reference range) or not. In total, 110 animals were included. The majority (85%) were ≥16 years (mean ± SD 19.8 ± 4.4 years); the most common breeds were Cob (18%), Thoroughbred (16%) and Welsh (15%); 37% were female and 63% male. Overall, 48% were compliant and 52% non-compliant. There was no significant effect of compliance on laboratory control. Of those that were compliant, 74% were controlled, while 67% of non-compliant animals were controlled. Univariable analysis revealed a significant (p < 0.001) effect of age and breed on compliance and control, and of sex on control. On multivariable analysis, only age (compliance) and breed (compliance and control) were retained in the final model. Only half of animals received the recommended pergolide dose; however, this did not affect laboratory control of PPID.

Should Pediatric Endocrinologists Consider More Carefully When to Perform a Stimulation Test?

IntroductionPediatric endocrinology rely greatly on hormone stimulation tests which demand time, money and effort. The knowledge of the pattern of pediatric endocrinology stimulation tests is therefore crucial to optimize resources and guide public health interventions. Aim of the study was to investigate the distribution of endocrine stimulation tests and the prevalence of pathological findings over a year and to explore whether single basal hormone concentrations could have saved unnecessary stimulation tests.MethodsRetrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 in a tertiary center.ResultsOverall, 278 tests were performed on 206 patients. The most performed test was arginine tolerance test (34%), followed by LHRH test (24%) and standard dose Synachthen test (19%), while the higher rate of pathological response was found in insulin tolerance test to detect growth hormone deficiency (81%), LHRH test to detect central precocious puberty (50%) and arginine tolerance test (41%). No cases of non-classical-congenital adrenal hyperplasia were diagnosed. While 29% of growth hormone deficient children who performed an insulin tolerance test had a pathological peak cortisol, none of them had central adrenal insufficiency confirmed at low dose Synacthen test. The use of basal hormone determinations could save up to 88% of standard dose Synachthen tests, 82% of arginine tolerance + GHRH test, 61% of LHRH test, 12% of tests for adrenal secretion.ConclusionThe use of single basal hormone concentrations could spare up to half of the tests, saving from 32,000 to 79,000 euros in 1 year. Apart from basal cortisol level <108 nmol/L to detect adrenal insufficiency and IGF-1 <-1.5 SDS to detect growth hormone deficiency, all the other cut-off for basal hormone determinations were found valid in order to spare unnecessary stimulation tests.

Factors Associated with Ovarian Hyperstimulation Syndrome (OHSS) Severity in Women With Polycystic Ovary Syndrome Undergoing IVF/ICSI.

IntroductionAge, polycystic ovary syndrome (PCOS), low body mass index (BMI), high antral follicle count (AFC), increased anti-Muller hormone (AMH) levels, and elevated serum estradiol (E2) concentrations are risk factors for ovarian hyperstimulation syndrome (OHSS). However, data on the relationship between risk factors and OHSS severity in patients with PCOS are rare.ObjectiveThis retrospective study examined the risk factors for OHSS and their effect on OHSS severity in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).MethodThe records of 2,699 women were reviewed and included in this study. These women were diagnosed with PCOS during their first IVF/ICSI cycle between January 2010 and December 2017. We analyzed the association between each of the interrogated risk factors (including female age, BMI, AFC, basal serum E2, and the number of oocytes retrieved) and OHSS. The effects of each risk factor on OHSS severity were further explored. Logistic regression was performed as part of the above analysis.ResultsOf the 2,699 women with PCOS who underwent assisted reproductive technology (ART), 75.2% had a normal response to controlled ovarian hyperstimulation (COH), while 24.8% developed OHSS. All OHSS patients were younger and had lower BMIs and basal serum follicle-stimulating hormone (FSH) and E2 levels but higher AFCs than those in the normal group. AFC demonstrated a strong correlation with OHSS, with a cutoff value of 24 in patients with PCOS. A total of 19.5% of the patients had mild OHSS, while 80.5% had moderate OHSS. Compared with those in the moderate OHSS group, those in the mild OHSS group were older and had higher basal serum FSH levels and lower serum E2 and T levels. However, BMI and AFC were not different between the mild and moderate OHSS groups. Basal serum E2 showed a strong correlation with OHSS severity, with a cutoff value of 37.94 pg/ml.ConclusionsAFC is a strong marker of OHSS, and basal serum E2 is the best predictor of OHSS severity in women with PCOS undergoing IVF treatment.

Impact of body mass index on intracytoplasmic sperm injection in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a condition that affects fertility. There are two types of PCOS; the normal/lean type and overweight/obese type. The aim of this study was to assess baseline characteristics, ovarian response, quality of oocytes, embryos, pregnancy, implantation and live birth rates in normal/lean and overweight/obese patients with PCOS undergoing ICSI compared with patients without PCOS. This retrospective case-control analytical study included 38 normal/lean and 17 overweight/obese patients with PCOS, and 98 normal/lean and 17 overweight/obese patients without PCOS. Parameters were observed based on baseline characteristics, ovarian response to dosage and duration of gonadotropin administered, number of oocytes, matured oocytes, fertilization rate, embryo quality and development, pregnancy, implantation and live birth rates. Basal serum luteinizing hormone in normal/lean PCOS was significantly higher compared with non-PCOS groups. Total dosage of gonadotropin used was significantly lower in normal/lean PCOS compared with other groups. End estradiol levels in normal/lean PCOS was significantly higher compared with the non-PCOS groups. Number of follicles, retrieved oocytes and matured oocytes were significantly higher in PCOS groups compared with the non-PCOS groups. However, there were no differences in fertilized oocytes, cleavage, number of top-quality embryos, pregnancy, implantation, and live birth rates among groups. This present study suggests that normal/lean PCOS requires lower gonadotropin dosages and that patients with PCOS have more follicles and oocytes compared with patients without PCOS, however the number of fertilized oocytes and embryos from patients with PCOS were the same as those from patients without PCOS and suggested that the quality of retrieved oocytes in PCOS might be compromised.

Progesterone levels predict pregnancy outcomes in individuals with fallopian tube associated infertility

BackgroundThis study aimed at determining the predictive value of human chorionic gonadotropin and progesterone levels on pregnancy outcomes in patients receiving in vitro fertilization due to fallopian tube associated infertility.MethodsWe retrospectively analyzed the clinical data of 854 cycles due to fallopian tube associated infertility in vitro fertilization fresh embryo transfer. The clinical data had been collected from January 2010 to December 2018 and was divided into 7 groups depending on the progesterone level on human chorionic gonadotropin administration day. Live birth rates and observation trends were calculated. The receiver operating characteristic curve was established to determine the optimal cutoff value for progesterone, which was used to further divide the data into 3 groups; Group 1 (progesterone ≦ 1.0 ng/ml), Group 2 (1.0 ng/ml ≤ progesterone ≤ 1.25 ng/ml), and Group 3 (progesterone ≥ 1.25 ng/ml). We then compared the ovulation results and clinical outcomes among the 3 groups.ResultsThere were no significant differences in age, infertility years, gonadotropin dosage, gonadotropin days, Luteinizing hormone level on human chorionic gonadotropin day, 2 pronuclear fertilization rates, clinical pregnancy rates, live birth rates, full-term birth rate, and preterm birth rates among the three groups. However body mass index (p = 0.001), basal luteinizing hormone (p = 0.034), estrogen peak (p < 0.001), number of oocytes obtained (P < 0.001) were significantly different.ConclusionsProgesterone level on human chorionic gonadotropin day does not affect the clinical pregnancy rate and live birth rates after in vitro fertilization. However, progesterone levels between 1.0 and 1.25 ng/ml may lead to good clinical pregnancy outcomes.

Do Basal Luteinizing Hormone and Luteinizing Hormone/ Follicle-Stimulating Hormone Ratio have Significance in Prognosticating the Outcome of In vitro Fertilization Cycles in Polycystic Ovary Syndrome?

Do Basal Luteinizing Hormone and Luteinizing Hormone/ Follicle-Stimulating Hormone Ratio have Significance in Prognosticating the Outcome of In vitro Fertilization Cycles in Polycystic Ovary Syndrome?