LH Supplementation for Low LH Levels during Antagonist IVF Cycles Improves Live Birth Rates

Introduction: Gonadotropin releasing hormone (GnRH) antagonist IVF protocols often induce a significant decrease in serum luteinizing hormone (LH) levels that may affect assisted reproductive technology cycle outcomes. However, supplementing all women undergoing antagonist cycles with recombinant LH does not improve clinical outcomes. The aim of this study was to assess the impact of LH supplementation specifically in those who had low intra-cycle LH levels. Methods: In this retrospective cohort study, women undergoing IVF/ICSI antagonist cycles had blood tests for LH, oestradiol and progesterone on day 5 of stimulation and then every 1-2 days until the trigger injection leading to egg collection. One group followed the current standard protocol of no LH supplementation given. The other had LH supplementation in the form of either recombinant LH (Luveris; Merck Serono, Switzerland) or urinary human chorionic gonadotropin (hCG) (Pregnyl; MSD, USA) when any intra-cycle blood test showed LH < 1 mIU/. Results: Between February 2010 and December 2011, 3 groups of women undergoing antagonist cycles were identified: (1) Cycles in which LH ≥ 1 (n = 81), (2) LH < 1 with no supplement given (n = 75) and (3) LH < 1 in which LH supplementation was given (n = 51). There were no significant differences in age, FSH starting dose, days of stimulation, number of embryos transferred, number of embryos frozen or endometrial thickness. Women given LH supplementation had significantly higher peak oestradiol levels. Live birth rates per cycle completed were (1) 43.2%, (2) 30.7% and (3) 45.1%. Women who had adequate LH or were supplemented during antagonist IVF cycles had a significantly better live birth rate (58/132) than women with low LH levels who were not given supplementation (24/75) (p < 0.05). Conclusion: This study, though relatively small, demonstrated significantly higher live birth rates in women given LH supplementation in antagonist cycles in which their intra-cycle LH levels were very low. Our monitoring indicates this occurs in over half of antagonist cycles. While there is ongoing debate about the potential benefit of LH supplementation, we propose that it is most likely to be useful when cycles are individualized and given when LH levels are shown to be low. More studies to examine this hypothesis are needed.