Recombinant LH supplementation during IVF cycles with a GnRH-antagonist in estimated poor responders: A cross-matched pilot investigation of the optimal daily dose and timing.

Although it is widely accepted that patients, who are considered poor responders to in vitro fertilization (IVF) benefit from recombinant luteinizing hormone (rLH) supplementation during an in vitro fertilization cycle, particularly when gonadotropin­releasing hormone (GnRH)­antagonist (ant) treatment is used the optimal administration timing and daily dose of rLH remains to be elucidated. The aim of the present study was to investigate the optimal timing of rLH­supplementation to improve ovarian response, embryo quality, endometrial thickness and pregnancy rate in infertile, estimated poor responders to IVF, undergoing GnRH­ant treatment. In addition, the present study aimed to evaluate the optimal daily dose to achieve the same outcomes. A prospective­randomized­cross­matched investigation was performed on 40 patients undergoing a GnRH­ant­treatment­cycle The patients were randomly assigned to either group A (rLH­75 IU/day) or group B (rLH­150 IU/day) and further randomized into subgroup A1/B1, in which rLH was administered at recombinant follicle stimulating hormone (rFSH) administration, and subgroup A2/B2, in which rLH was administered at GnRH­ant administration. Patients who did not become pregnant during the first cycle (35 patients), were treated a second time, cross­matched for groups and subgroups. Improved ovarian response, embryo quality and pregnancy rate were achieved by administering rLH at 150 IU/day, starting from GnRH­ant administration, independently from the total rLH dose administered. Improved endometrial thickness at oocyte retrieval day was achieved by administering rLH at 150 IU from the start of rFSH administration. These data led to the hypothesis that ovarian responses are affected by the timing of administration more than the total­dose of rLH. The optimal window to administer rLH appears to be the mid­to­late follicular phase, despite the fact that rLH­supplementation in the early­follicular phase appeared to increase endometrial thickness and to enhance its morphology. Standardization of the optimal daily dose and supplementation timing of rLH may resolve the debate regarding its efficacy in increasing the number of pregnancies and neonatal survival rates.