Developments on Mammalian Oocyte Maturation Using ZHB112-113, a Novel Long-Acting Human FSH and LH Recombinant Fusion Protein†.

Use of luteinizing hormone in the treatment of infertility: time for reassessment?

Novel follicular-phase gonadotropin-releasing hormone antagonist stimulation protocol for in vitro fertilization in the poor responder

Ovarian stimulation and fertility preservation with the use of aromatase inhibitors in women with breast cancer

Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women

Ovarian stimulation is an integral part of assisted reproductive technologies (ART). Under physiologic conditions, both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity is necessary to guarantee follicle growth and maturation. This can be shown in patients with hypogonadotrophic hypogonadism, who have no endogenous FSH or LH activity. The use of FSH alone in these patients does not result in sufficient follicle growth and oocyte quality. Approximately 75IU of LH activity per day is necessary to guarantee optimal success. The use of gonadotropin-releasing hormone (GnRH) agonists in normogonadotrophic patients may result in suppression of LH levels below a certain threshold, resulting in suboptimal outcomes. The question under discussion in this article is the threshold level of LH below which exogenous LH activity should be added to provide optimal ovarian response. Different studies indicate that the endogenous LH level should be 0.5-1.5IU in long-term protocol situations. Patients treated in ultra-long GnRH agonist protocols, as well as older patients, patients with a low response to gonadotropin treatment, and patients treated with a GnRH antagonist protocol may benefit from exogenous LH activity. There are three ways of adding LH activity in ovarian stimulation cycles. Nowadays, lutropin alfa (recombinant LH) may be the optimal choice since it has no chorionic gonadotropin activity and allows individual dosage titration. Every menotropin preparation currently on the market contains some chorionic gonadotropin activity. However, more data are necessary before evidence-based recommendations regarding LH supplementation in ovarian stimulation protocols can be given.

Enough is enough! Patients who do not conceive on 600 IU/d of gonadotropins show no improvement from an additional 150 IU of LH activity

Follicle-stimulating hormone (FSH) and luteinising hormone (LH) act in concert in the stimulation of folliculogenesis and ovulation. However, high levels of LH promote follicular atresia and early miscarriage, and this has led to the concept of a 'therapeutic window' of LH for successful conception in assisted reproductive technology (ART) and ovulation induction. Until now, urinary-derived human menopausal gonadotropin (hMG) has been the only available source of exogenous LH activity. hMG preparations contain highly variable levels of LH, and are often augmented with human chorionic gonadotropin (hCG), which mimics LH activity. Accumulation of hCG bioactivity, however, may have detrimental effects on follicular development and oocyte quality. Recombinant human LH (r-hLH) (Luveris) is the only pure source of LH activity. r-hLH is well characterised and production is tightly controlled, resulting in a highly consistent product. Clinical studies in hypogonadotropic hypogonadal women have demonstrated the efficacy of r-hLH, 75 IU/day, together with r-hFSH, 150 IU/day, in promoting optimal follicular development, oestrogen secretion and endometrial thickness. r-hLH therefore provides the clinician with the opportunity for precise and consistent dosing within the therapeutic window for patients requiring exogenous LH, without the risk of LH overexposure that is associated with hCG.

Gonadotropin-releasing hormone (GnRH)-agonist versus GnRH-antagonist in ovarian stimulation for assisted reproductive techniques: Results of a prospective randomized trial

Current opinion on use of luteinizing hormone supplementation in assisted reproduction therapy: an Asian perspective

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 > 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.

Aging and infertility in women: a committee opinion

Comparison of metaphase II oocytes after stimulation with recombinant follicle-stimulating hormone and urinary follicle-stimulating hormone in a pituitary down-regulation regimen

Role of LH and FSH in ovarian function

Recombinant luteinizing hormone in assisted reproductive technology

O-298: In vitro maturation, in vitro fertilization and embryo transfer (IVM-IVF) combined with low dose FSH over Metformin pretreatment and frozen-thawed cycles should be a routine ART option for polycystic ovarian syndrome (PCOS) patients