Exogenous Luteinizing Hormone Research Articles

PSIV-17 Postnatal Obesity Amplifies Gnrh-Induced Lh Release in Prenatal Testosterone-Treated Female Sheep

Abstract Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in females of reproductive age. Hypersecretion of luteinizing hormone (LH), partly due to increased pituitary sensitivity to gonadotrophin-releasing hormone (GnRH), is a significant cause of infertility in women with PCOS. Moreover, obesity amplifies the severity of reproductive dysfunction in PCOS. In sheep, testosterone (T) excess during gestational days (GD) 30 to 90 results in GnRH-mediated LH hypersecretion and recapitulates the PCOS phenotype. This study investigated 1) if mid-gestation (GD 60 to 90) is the susceptibility window for programming pituitary hypersensitivity to GnRH, and 2) the contribution of postnatal obesity in modulating LH responsiveness to GnRH. Suffolk ewes received T propionate (T; 100 mg i.m.) or corn oil (C; vehicle) twice weekly from GD 60 to 90 (term = 147 d). At 5 mo of age, T lambs were assigned randomly to either a maintenance (100% of NRC requirements) or overfed diet (130% of NRC requirements), and Control lambs were fed the maintenance diet. During the anestrous period (late summer), ewes (n = 8/group; ~17 mo of age) received a GnRH bolus injection (2 ng/kg) intravenously every 1.5 h and blood samples were collected at 15-min intervals for a 6-h period. Despite animals being in seasonal anestrous, few endogenous LH pulses were evident during the 6 h-sampling period. To avoid confounding, only clear responses to GnRH challenge that occurred within 15 to 45 min after each GnRH injection were considered for further analyses. Mean number of exogenous GnRH-induced LH responses that met these criteria did not differ between groups and averaged 1.81 ± 0.27 pulses/animal. The parameters of these GnRH-induced responses were analyzed as one-way ANOVA with Tukey’s HSD post-hoc analysis. Mean LH pulse peak was greater (P < 0.05) in T overfed ewes (4.59 ± 0.49 ng/mL) compared with T maintenance (2.19 ± 0.61 ng/mL) and Control ewes (2.58 ± 0.53 ng/mL). Additionally, amplitude of LH pulses was greater (P < 0.05) in T overfed ewes (2.66 ± 0.39 ng/mL) compared with T maintenance (1.03 ± 0.48 ng/mL) and tended (P = 0.089) to be greater in T overfed compared with Control ewes (1.41 ± 0.42 ng/mL). LH pulse peak and amplitude in T maintenance did not differ from Control ewes. In conclusion, failure of GD 60 to 90 T treatment to increase GnRH responsiveness as opposed to our earlier finding of increased responsiveness in GD 30 to 90 T-treaded sheep indicates that the susceptibility window for programming pituitary hypersensitivity to GnRH lies between GD 30 to 60. Postnatal obesity may act as an independent activational signal in amplifying the pituitary sensitivity to GnRH in female sheep. This premise is supported by observations that obesity exacerbates pituitary-mediated LH hypersecretion in women with PCOS. Research support: NIH-NICHD (R01HD099096).

Effects of Low Luteinizing Hormone Serum Levels on Oocyte Retrieval, Fertilization Rate, and Embryo Quality during Controlled Ovarian Stimulation: Results from a Prospective Cohort Analysis

Objectives: Luteinizing hormone (LH) plays a key role in normal follicular development and oocyte maturation in controlled ovarian stimulation. LH stimulates the proliferation and differentiation of theca cells for the secretion of androgens, synergistically increasing estrogen production. This study aimed to investigate the effects of low LH concentrations on oocyte retrieval, fertilization, and embryo development in patients undergoing in vitro fertilization/intracytoplasmic sperm injection. Design: We prospectively (ClinicalTrials ID: NCT05755529) analyzed patients undergoing in vitro fertilization/intracytoplasmic sperm injection, subdividing them into three groups according to their age. Serum LH levels were evaluated on day 3, during stimulation (day 10) and before ovulation induction (day 12). Participants/Materials, Setting, Methods: Forty-three consecutive women were scheduled for IVF and received ovarian stimulation with follitropin alfa (Gonal F, Merck Serono, Germany) and ganirelix (Fyremaldel, Sun Pharma, Italy). Statistical analysis was performed with InStat 3.10, GraphPad software, San Diego, CA, USA. Normal distribution was tested by the Shapiro-Wilk test. Continuous variables were expressed as the mean and standard deviation. Categorical variables are expressed as frequencies and percentages. Results: Our data analysis suggests that serum LH levels progressively decrease during controlled ovarian stimulation, and this effect is more evident in the early phase of this procedure. From this perspective, circulating LH levels may significantly decrease during the late follicular phase due to the negative feedback of ovarian hormones from multiple follicular developments or after the suppressive effects of gonadotropin-releasing hormone antagonists. Limitations: Although our study confirms that exogenous LH can be considered a strategy in women with reduced LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome, the generalizability of the results is limited by the low number of participants enrolled. Conclusions: Exogenous LH may be considered a strategy in women with a decrease in LH levels during ovarian stimulation to improve oocyte quality and reproductive outcome.

P-397 The effect of letrozole overlapped with gonadotropin on IVF outcomes in women with DOR or aged over 40 years old

Abstract Study question Evaluating the efficacy of modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced age women. Summary answer The modified letrozole protocol provides another option for women with DOR or advanced age, especially those who experienced ovarian stimulation previously. What is known already For years, numerous methods have been conducted to obtain better outcomes in women with advanced age or DOR. Increasing doses of gonadotropin (Gn), exogenous luteinizing hormone (LH) or growth factor (GH) supplementation, and various kinds of controlled ovarian stimulation (COS) protocols were reported. However, there is still no consensus due to the contradictory reports of comparable reproductive outcomes. During ovarian stimulation, estrogen and androgen are important in the recruitment of primordial follicles and promotion of follicular growth at the preantral and antral stages across different species. Study design, size, duration This is a paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. Participants/materials, setting, methods 123 women received stimulation with mLP. GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. Clinical pregnancy rate (CPR) and cumulative clinical pregnancy rate (CCPR) were main outcomes. Main results and the role of chance CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.01%, respectively. In women with repeated cycles, mLP achieved higher available embryo rate and top-quality embryo rate. Further study showed positive correlation between testosterone and the number of oocytes retrieved in mLP group (r = 0.395, P< 0.01). Limitations, reasons for caution It is a retrospective study which resulted in minor bias among mLP and the other control protocols. Although we have already paired for age and AMH, the presence of biases cannot be totally excluded. Further prospective studies need to be done to validate the effect of mLP. Wider implications of the findings The modified letrozole protocol may be effective for women with DOR or advanced age, especially those who have experienced previous cycle failure. An increasing serum testosterone level may play a role and reflect follicular growth during ovarian stimulation. Trial registration number not applicable

Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH

Keratoconus (KC) affects the corneal structure, with thinning and bulging outward into a conelike shape. Irregular astigmatism and decreased visual acuity appear during puberty and progress into the mid-30s, with unpredictable disease severity. The cause of KC is recognized as multifactorial, but remains poorly understood. Hormone imbalances are a significant modulator of the onset of KC. This study sought to investigate the role of gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in KC, using a three-dimensional, self-assembled matrix invitro model. Healthy corneal fibroblasts and human KC cells in the corneal stroma were isolated, cultured, and stimulated with stable vitamin C to promote extracellular matrix assembly. Cultures were further stimulated with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH. Samples were evaluated for cell proliferation and morphology via BrdU assay and imaging; protein expression was assessed via Western blot analysis. Proliferation was significantly greater in human KC cells compared to healthy corneal fibroblasts with LH stimulation, but no changes were found with FSH stimulation. Additionally, in sex hormone receptors, fibrotic markers, proteoglycans, and members of the gonadotropin signaling pathway were significantly changed, largely driven by exogenous LH. The impact of exogenous FSH/LH in the KC stromal microenvironment was demonstrated. These results highlight the need to further examine the role of FSH/LH in KC and in human corneal homeostasis.

Effect of Exogenous Luteinizing Hormone (LH) Supplementation on Clinical Pregnancy of Patients Receiving Long-Acting Gonadotropin-Releasing Hormone Agonist (GnRHa) Cycles: A Retrospective Cohort Study.

Timely and moderate luteinizing hormone (LH) secretion plays critical roles in follicle development and maturation. However, the role of LH supplementation in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles remains unclear. Can LH supplementation improve the clinical outcomes of patients who receive long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation in IVF/ICSI-ET cycles? This is a retrospective cohort study of 2600 long-acting GnRHa down-regulated IVF/ICSI cycles from 2017 to 2020 in our reproductive medicine centre of Nanjing Drum Tower Hospital. Total cycles were divided into two groups according to LH supplementation or not. In addition, we conducted a secondary analysis that used propensity-score matching to reduce the effects of confounding. Exogenous LH addition was not significantly correlated with the clinical pregnancy rate (OR=0.910, 95% CI: 0.623-1.311, p=0.61) in logistic regression analysis. After propensity-score matching, we also found no significant association between LH supplementation and the clinical pregnancy rate (OR=0.792, 95% CI: 0.527-1.191, p=0.26). There is no obvious effect of exogenous LH supplementation on the clinical pregnancy rate in non-selective patients receiving long-acting GnRHa IVF/ICSI-ET cycles, which suggests that exogenous LH addition is not always needed, which can help us avoid drug overuse to a certain extent.

Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review.

The management of infertile women affected by hypogonadotropic hypogonadism (HH) or conditions mimicking it is particularly challenging. In the present narrative review, we aimed to synthesize the available evidence on the benefit (if any) of exogenous luteinizing hormone (LH) supplementation in this group of patients. Available data support LH supplementation in women with organic or functional HH. On the contrary, the benefit of exogenous LH on reproductive outcomes both in advanced maternal age patients and in cases of depletion of FSH and LH levels induced by GnRH analogues has not been demonstrated. unfortunately, the inhomogeneous study populations as well as the methodological heterogeneity between studies focused on women affected by conditions mimicking HH do not allow reliable conclusions to be drawn.

Novel roles of luteinizing hormone (LH) in tissue regeneration-associated functions in endometrial stem cells

Luteinizing hormone (LH) stimulates the synthesis and secretion of the key steroid hormone estrogen, which subsequently promotes ovarian follicular growth and development. Therefore, the administration of exogenous LH to achieve superovulation (multiple ovulations) and an LH surge is commonly used as the most effective therapeutic option in a majority of in vitro fertilization (IVF) clinics. However, a relatively low pregnancy rate (between 20% and 35%) is one of the most challenging aspects of LH-based infertility treatment. Furthermore, the major cause of this low pregnancy rate in LH-based infertility treatment remains unidentified. Recent studies have shown that endometrial stem cell loss or deficiency can significantly decrease tissue regeneration ability during the menstrual cycle and reduce endometrial receptivity. In this context, we postulated that the low pregnancy rates following LH-based ovarian hyperactivation may be the result of the adverse effects of consecutive exogenous LH administration on endometrial stem cells. To the best of our knowledge, this study revealed for the first time that in addition to its previously reported roles in stimulating ovarian functions through the pituitary-gonadal axis, LH brings about the extragonadal suppression of various tissue regeneration-associated functions in endometrial stem cells, such as self-renewal, migration ability, multilineage differentiation potential, and pluripotency/stemness, by inhibiting pro-survival Akt and ERK1/2 signaling pathways in vitro and in vivo, and as a consequence, it decreases the endometrial receptivity.

Application of Exogenous Luteinizing Hormone in IVF Patients of Late Reproductive Age

Application of Exogenous Luteinizing Hormone in IVF Patients of Late Reproductive Age

Exogenous luteinizing hormone promotes ovarian survival and function during cryopreservation and transplantation

Cryopreservation and transplantation of the ovarian tissue is an alternative method by which malignant tumor survivors can recover fertility. Previously, it was reported that follicle stimulating hormone (FSH) promoted the survival and functioning of the ovarian tissue after in vitro cultivation. In this study, the expression of the luteinizing hormone receptor (LHR) was observed on the granule cell membrane after luteinizing hormone (LH) (0.3 IU/mL) was supplied as an exogenous hormone into the cultivation medium during ovarian vitrification in the postnatal period (PND) (1, 7, 14, 21, 28, 42, and 56 days PND). The expression of vascular endothelial growth factor (VEGF) and Connexins (Cx), and the recovery of ovarian functions were then assessed in mice models. The results showed that LH increased the production of normal follicles, and upregulated the expression of VEGF, Cx37, and Cx43 in vitrified ovaries. LH administration also shortened the recovery time of the estrus cycle in mice models. Additionally, no difference was observed in the rate of pregnancy and size of the first litter between the experimental and control groups. In conclusion, LH could promote the survival and functioning of the ovaries by upregulating the expression of VEGF, Cx43, and Cx37 during ovarian cryopreservation and transplantation.

The ratio of exogenous Luteinizing hormone to Follicle stimulating hormone administered for controlled ovarian stimulation is associated with oocytes' number and competence.

We performed a retrospective study aiming to study the relationship between the ratio of the exogenous luteinizing hormone to follicle stimulating hormone (LH/FSH) administrated for controlled ovarian stimulation (COS) and the number and competence of the oocytes retrieved for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Eight hundred sixty-eight consecutive infertile patients (mean age 34.54 ± 4.01 years, mean anti-Müllerian hormone (AMH) 2.94 ± 2.07 ng/ml) treated with long agonist protocol and a mixed gonadotropin protocol (human menopausal gonadotropin in association with recombinant FSH (recFSH)) who performed IVF/ICSI between January 2013 and February 2016, were included. Patients with severe male factor were excluded. LH/FSH was calculated based on total doses of the two gonadotropins. We found, after adjustment for confounders, a positive relationship between LH/FSH and the retrieved oocytes’ (β = 0.229, P<0.0001) and zygotes’ number (β = 0.144, P<0.0001) in the entire study group and in subgroups according to age (<35 and ≥35 years) and ovarian reserve (AMH < 1.1 and ≥ 1.1 ng/ml). The fertilization rate was positively associated with LH/FSH in patients with LH/FSH in the lowest three quartiles (below 0.77) (β = 0.096, P=0.034). However, patients in the fourth quartile of LH/FSH had a lower fertilization rate as compared with patients in quartiles 1–3 which, after adjustment for covariates, was only marginally negatively related with LH/FSH (β = −0.108, P=0.05). In conclusion, our results suggest that the adequate LH/FSH administrated during COS can improve the oocytes’ and zygotes’ number in IVF/ICSI cycles, but also the fertilization rate when a certain proportion of LH/FSH is not exceeded.

Luteinizing hormone changes in gonadotropin-releasing hormone antagonist protocol in in vitro fertilization cycles: A cross-sectional study.

BackgroundBecause of the unexpected and often dramatic inhibition of luteinizing hormone (LH) secretion related with the usage of gonadotropin-releasing hormone (GnRH)-antagonist, there has been a probable need for exogenous LH supplementation. There is a basic and clinical evidences that show late development of follicle needs an LH but there is a threshold for LH requirements during folliculogenesis.ObjectiveThe purpose of this study was to evaluate the changes in serum LH and the identification of patients who benefit from the addition of LH.Materials and MethodsSeventy volunteers for antagonist protocol in IVF cycle were enrolled in this prospective cross-sectional study. The study was carried out in Reproductive Health Research Center, University of Medical Sciences between July 2016 and February 2016. Serum LH level was estimated 24 h before and after the first (GnRH) antagonist injection. The primary outcome was the serum level of LH and its change in the three groups and the secondary outcome was Egg and Embryo quality.ResultsLH changes above or below 50% had no effect on the number of follicle, the number of oocyte, Germinal vesicle oocyte, metaphase 1 oocyte, metaphase 2 oocyte, endometrial thickness, and chemical and clinical pregnancy.ConclusionWe evaluated the changes of serum LH in the patients who were entered in the antagonist protocol. Our study showed no significant difference in LH levels 24 h before and after the injection of the antagonist between the three groups, and LH changes did not affect the outcome of pregnancy.

Androgen Regulation in Spermatogenesis to Increase Male Fertility

&lt;p class="00-6Abstrak2Wtz"&gt;Male fertility is affected by quantity and quality of sperm which controlled by androgens (testosterone and 5α-dihydrotestosterone) mediated by androgen receptors (AR). Androgen receptors belong to receptor group of steroid hormone and a group of ligand-activated nuclear receptor superfamily. This paper explains androgen hormone and its regulation in spermatogenesis to increase male fertility. Regulation of androgen hormone in spermatogenesis include initiation of spermatogenesis, proliferation and maturation of Sertoli cells, germ cell development, spermatogonia, meiosis, and spermiogenesis. The role of androgen hormone in regulation of spermatogenesis is influenced by AR, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels. Disruption of spermatogenesis will cause low male fertility. However, low concentrations of AR, LH and FSH could be enhanced by exogenous gonadotrophine releasing hormone (GnRH), LH, FSH, and testosterone to increase male fertility.&lt;/p&gt;

The impact of luteinizing hormone supplementation in gonadotropin-releasing hormone antagonist cycles: a retrospective cohort study

The impact of exogenous luteinizing hormone (LH) supplementation to patients undergoing controlled ovarian stimulation with gonadotropin-releasing hormone (GnRH) antagonists on cycle outcomes is controversial. Here, we present a retrospective cohort study including cycles from December 2015 to December 2016. Totally 320 cycles were divided into two groups according to with or without exogenous LH supplementation. No significant differences regarding the number of retrieved oocytes, the number of good-quality embryos, and clinical pregnancy rate between the two groups were found. The logistic regression analysis revealed that LH supplementation was not independently associated with clinical pregnancy rate (OR = 0.577, 95% CI: 0.272–1.222, p = .58) or a biochemical pregnancy rate (OR = 0.922, 95% CI: 0.444–1.916, p = .83). When patients were divided into subgroups based on age, more retrieved oocytes (5.60 vs. 3.97, p = .04) and good-quality embryos (3.07 vs. 1.93, p = .01) were achieved in cycles with exogenous LH supplementation for 40 years and over group. We conclude that for aged women (40 years old and over), LH supplementation has a positive impact on the number of retrieved oocytes and good-quality embryos in GnRH antagonist cycles.

AB68. Novel regulators of testosterone production

In recent years, interest in testosterone replacement therapy for the management of male hypogonadism has grown significantly. This development has paralleled increased public awareness of the signs and symptoms of hypogonadism (also known as low T or low serum testosterone) and the opportunity to address this problem with therapeutic interventions. Conventionally, medical treatment of hypogonadism has been met with various formulations of exogenous testosterone therapies, albeit such therapies do carry limitations. Limitations range from challenges with therapeutic delivery to possible adverse effects. As understanding has grown with respect to regulatory mechanisms of testosterone production and possible new targets for endogenous production of testosterone, new avenues are opening for consideration of therapy particularly in males with primary hypogonadism (low intratesticular testosterone, high serum luteinizing hormone (LH) with low serum testosterone). Several novel molecular pathways have received interest recently as potential pharmacologic targets to increase Leydig cell testosterone production. These pathways and/or signaling molecules include phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin. The advantages of these new targets are suggested to be: (I) maintain an intratesticular testosterone environment that allows /promotes normal spermatogenesis, (II) avoid side effects of exogenous testosterone supplementation, and (III) maintain the negative feedback mechanism of luteinizing hormone (LH) that prevents testosterone levels from becoming supratherapeutic. These novel options are perceived to offer a more targeted and efficacious approach than other suggested interventions to stimulate Leydig cell testosterone production in individuals with primary hypogonadism, such as exogenous LH, human chorionic gonadotropin, and clomiphene, which all act conventionally through the LH receptor. The proposed novel targets offer opportunities to promote increased endogenous testosterone production through the Leydig cell directly without reliance upon functional LH receptors. This approach may involve the application of small molecules, dietary supplements, or even currently available FDA- approved medications, that may exploit newly refined understanding of signaling pathways at the Leydig cell level. It will be of interest to study all of these potential therapeutic prospects further both with careful animal model experimentation and subsequently in human clinical trials.

Luteal phase dynamics of follicle‐stimulating and luteinizing hormones in obese and normal weight women

Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to gonadotrophin-releasing hormone (GnRH) in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous luteinizing hormone (LH) in obese women. Participants underwent a luteal phase frequent blood sampling study. Endogenous LH pulsatility was observed, gonadotrophin-releasing hormone (GnRH) was given in two weight-based doses, and GnRH antagonist was administered followed by recombinant LH. Regularly menstruating obese (n = 10) and normal weight (n = 10) women. Endogenous hypothalamic-pituitary function (as measured by LH pulsatility), pituitary sensitivity (GnRH-induced LH secretion), pharmacodynamics of endogenous LH and pharmacokinetics of exogenous LH were compared between the obese and normal weight groups. There were no statistically significant differences in endogenous LH pulsatility or pituitary responses to two weight-based doses of GnRH between the obese and normal weight women. There were no differences in the pharmacodynamics of endogenous LH or the pharmacokinetics of exogenous LH between the groups. FSH dynamics did not differ between the groups throughout the study. The relative hypogonadotrophic hypogonadism of obesity cannot be explained by differences in LH and FSH luteal phase dynamics or differences in endogenous LH pharmacodynamics or exogenous LH pharmacokinetics.

Luteinizing Hormone in Controlled Ovarian Stimulation

ABSTRACTThe role of follicle stimulating hormone (FSH) in assisted reproductive technology is well understood, though there is still no published consensus on the need for exogenous luteinizing hormone (LH) in controlled ovarian stimulation. There is a dilemma regarding the usefulness of LH supplementation in controlled ovarian stimulation despite growing understanding of the LH and FSH interrelation and their effects on fertilization and implantation. This review revisits the physiological role of LH, LH receptors and the concept of LH therapeutic window. With the availability of LH activity from different sources, there is a need to understand the differences between recombinant human LH (r-HLH), human menopausal gonadotropin and human chorionic gonadotropin (hCG). It has been observed that adjuvant r-HLH provides precise control over the dose of LH bioactivity administered to target the therapeutic window. This review discusses about the various patient subgroups that may benefit from LH supplementation. The use of r-HLH is recommended in women with poor response in a previous cycle or suboptimal follicular growth in an ongoing ovarian stimulation cycle by day 6 to 8 of stimulation. Exogenous LH administration should also be considered in women at risk of suboptimal response, specifically age &gt; 35 years and women treated with GnRH analogues (agonists or antagonists) during ovarian stimulation causing over suppression of endogenous LH and FSH pituitary secretion. Further research is needed to identify LH polymorphisms, adequate dosing, cost efficacy, need for rLH and hCG supplementation in different patient profiles for maximum benefit during controlled ovarian stimulating (COS).How to cite this articleVohra A, Rao KA. Luteinizing Hormone in Controlled Ovarian Stimulation. Int J Infertil Fetal Med 2014; 5(3):75-86.

A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology

BackgroundFollicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice.MethodsA 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS).ResultsIn total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%).ConclusionsIn German routine clinical practice, the most common reasons for using the 2:1 formulation of follitropin alfa and lutropin alfa for women undergoing ART were POR, low baseline LH, and age. Severe OHSS incidence was low and similar to that reported previously.Trial registrationClinicaltrials.gov NCT01112618

Examining sources of variation in HPG axis function among individuals and populations of the dark-eyed junco

Gonadal steroids are important mediators of traits relevant to fitness, and thus may be targets of selection. However, more knowledge is needed about sources of variation along the endocrine axes that may contribute to functional variation in steroid levels. In a controlled captive environment, we studied males of two closely related subspecies of the dark-eyed junco (Junco hyemalis) that differ in testosterone-related phenotype, asking whether they also differ in testosterone (T), and assessing the contribution of the sequential links of the hypothalamic–pituitary–gonadal axis. When males of both subspecies were challenged with gonadotropin-releasing hormone (GnRH), they were similar in circulating luteinizing hormone (LH) and T responses. When challenged with exogenous LH, they again produced levels of T similar to one another, and to the levels produced in response to GnRH. However, the smaller, less ornamented, and less aggressive subspecies had greater abundance of mRNA for LH receptor in the testes and for androgen receptor in the rostral hypothalamus, suggesting potential differences in regulatory feedback. We suggest that circulating hormone levels may be less prone to evolutionary change than the responsiveness of individual hormone targets. Among individuals, T titers were highly repeatable whether males were challenged with GnRH or with LH, but LH produced in response to GnRH did not covary with T produced in response to LH. Testis mass, but not LH receptor transcript abundance, predicted individual variation in T responses. These data implicate the gonad, but not the pituitary, as an important source of individual variation in T production.

The clinical effect of LH supplementation in controlled ovarian stimulation

In spite of previous reports on the beneficial effects of adding exogenous luteinizing hormone (LH) activity to gonadotropin releasing hormone (GnRH) agonist long protocols for conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), these effects in various age groups are still controversial. This study was performed to evaluate the clinical efficacy of adding LH activity to GnRH agonist long protocols according to patient's age.

Influence of Lineage, Broodstock Conditioning, and Hormone Injection on Gila Trout Reproductive Success and Egg Fatty Acid Composition

AbstractSuccessful reproduction of captive‐reared fishes depends on hatchery practices and proper broodstock nutrition. Nutrient requirements and environmental conditions stimulating reproductive development are unknown for many threatened and endangered species and may differ between lineages within species. Accordingly, prior to spawning, Main Diamond Gila Trout Oncorhynchus gilae broodstock were exposed to different thermal cycles and hormonal injection to improve reproductive success. Additionally, egg fatty acid composition and hatching success of Main and South Diamond Gila Trout were evaluated to determine the extent of phenotypic differences between lineages. Thermal conditioning of broodstock accompanied with injections of exogenous luteinizing hormone releasing hormone analog (LHRHa) prior to spawning improved progeny survival over historic hatchery means as well as means for broodstock reared in raceways at constant temperatures without LHRHa. Egg n‐6 fatty acid content appears to be associated with this improvement. Eggs from Main and South Diamond broodstock fed the same feeds had similar hatch rates but could be differentiated on the basis of fatty acid profile. Future trials should further evaluate the influence of dietary fatty acids on egg deposition and hatch rate, while acknowledging that changes in reproductive performance may differ across lineages. Broodstocks should continue to be conditioned with thermal cycling and use of LHRHa to induce ovulation, as these techniques resulted in significantly better hatch rates in the current study than use of only photoperiod manipulation to stimulate reproductive development.