Clinical Research Directory

Extended LH Administration

Sponsor: Azienda Ospedaliero-Universitaria di Modena

Summary

Luteinizing hormone (LH) plays an important role in follicular development, especially in the later stages of folliculogenesis. Theca interstitial cells and, later, granulosa cells express high concentrations of receptors for LH (LH-R). LH modulates the progressive remodeling and growth of the follicle . New evidence points to a role for LH in promoting ovarian follicle growth and maturation, even at very early stages of folliculogenesis. Studies analyzing LH-R expression profiles in the ovary have shown that LH-R is moderately expressed even in the smallest follicles, during what is known as the gonadotropin-independent phase . Immunohistochemical studies that examined the localization of LH-R in human follicles through different stages of follicular development reveal that LH-R is expressed by granulosa cells and some thecal cells in small pre-antral follicles LH promotes the transition of follicles to the antral stage, thus leading to an increase in functional ovarian reserve. Early follicular stages, particularly those between the primordial and pre-antral stages, are critical as they regulate the rate of follicle recruitment. The potential roles of LH in the early follicular phase were analyzed in a prospective, randomized multicenter study using a sequential approach to stimulation with recombinant human r-LH, followed by r-FSH, in women in hypogonadotropic hypogonadism because they were profoundly down-regulated by the administration of depo agonist GnRH analog. LH treatment was associated with an increase in small antral follicles before FSH stimulation and a higher number of normally fertilized embryos. In addition, AMH hormone was found to be significantly increased in both groups during the week prior to FSH stimulation These results seem to indicate that, if the reduction in the number of antral follicles is not due to a decrease in the number of primordial follicles, but to a slowing of progression, as in the case of women with long-standing hypothalamic amenorrhea, there may be room for a therapeutic approach. This is with the aim of improving the response to ovarian stimulation of the aforementioned patients who present with anovulatory cycles and in a condition of hypogonadotropic hypogonadism. A recent case series described two patients suffering from hypothalamic amenorrhea with very low levels of endogenous gonadotropins, and ovulatory factor infertility. These patients were treated with exogenous LH for one to two months (prolonged administration of LH). Increased levels of both AMH and AFC were demonstrated, and they responded adequately to ovarian stimulation. The purpose of this multicenter prospective randomized study follows recent publications confirming the implementation of ovarian reserve by supplementation with pretreatment with r-LH, a drug already on the market and routinely used in conventional controlled ovarian stimulation protocols. The aim is to confirm that pretreatment with rhLH at a dose of 185.5 IU/day for 60 days can improve ovarian reserve, as indicated by increased baseline AMH and AFC, compared with no pretreatment. The primary outcome is serum AMH value after treatment with r-LH and without. The planned duration of the study is 18 months, and a total of 84 patients are to be recruited. Patients will be randomized into two groups: group A who will receive pre-treatment with r-LH 185.5IU/day for 60 days and group B who will not receive pre-treatment. Patients will have a monitoring visit every two weeks for the duration of treatment, during which an ultrasound and blood sampling will be performed to evaluate the hormonal picture. Following pretreatment, a visit of with assessment of serum AMH and AFC value will be performed and the planned IVF cycle will be started. This will be followed by an additional final follow-up visit to collect obstetric and newborn outcomes that will be conducted by telephone

Official title: Extended LH Administration (ELHA), a Strategy to Increase the Pool of Recruitable Antral Follicles: a Multicentric Randomized Trial

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