Objective:Is a single dose of gonadotropin-releasing hormone agonist (GnRHa) trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization (IVF) cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity?Design:This is a prospective, randomized, double-blind, proof-of-concept study.Setting:This study was carried out at a tertiary care center.Material and Methods:A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003) undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH), progesterone (P4), and follicle-stimulating hormone (FSH) values were estimated.Statistical Analysis:Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity.Main Outcome Measures:Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L), FSH (IU/L), and P4 (ng/mL) levels implantation rate and clinical pregnancy rate.Results:A higher number of mature (metaphase II) oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0.57; P < 0.01). Significantly a higher number of blastocysts were obtained in Group B than Group A (4.00 vs. 3.04; P = 0.023). The odds of clinical pregnancy per patient were higher in Group B (OR = 0.56; CI [0.27–1.24]), with a trend towards better clinical pregnancy in Group B than in Group A.Conclusions:A repeat dose of GnRHa trigger 12 h following the first dose probably by maintaining a sustained level of gonadotropins yielded a better maturity of oocytes, higher number of blastocysts, and a trend towards higher clinical pregnancy than a single dose in PCOS patients undergoing IVF in antagonist cycles.
Objective: The use of Gonadotrophin releasing hormone agonist (GnRHa), with freeze-all strategy followed by frozen embryo transfer (FET) has been found to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF cycles. However, physicians still hesitate to routinely use GnRHa as a trigger, replacing human chorionic gonadotrophin (hCG), for concerns of compromised cycle outcome. We aimed to evaluate outcomes following the transfer of embryos in FET cycles obtained from GnRHa trigger in comparison with hCG trigger in PCOS patients of Asian origin. Methods: Prospective observational cohort study. 210 PCOS patients undergoing IVF in an antagonist protocol who were randomized in the previous study (to evaluate if GnRHa trigger is a better alternative than hCG in PCOS patients to prevent OHSS; Group A: GnRHa trigger (n=92)] and Group B: hCG trigger (n=101)], were followed up in FET cycles to assess the outcomes. Results: The odds of cumulative live birth rate per stimulation cycle favors GnRHa trigger against the hCG trigger [OR=2.15; (CI 1.2-3.83); p=0.008]. A significantly higher number of mature oocytes (19.1±11.7 versus 14.1±4.3; p<0.001) and blastocysts (4.2±1.63 versus 3.26±1.22; p<0.001) were available in the GnRHa group as compared to the hCG group. Conclusion: The cumulative live birth rate was better following transfer of frozen-thawed embryos generated from GnRHa-triggered cycles compared to hCG trigger. Hence, in PCOS undergoing IVF, as a good practice point, hCG trigger should be replaced by a GnRHa trigger with vitrification of all embryos followed by FET.
The 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 article Vohra A, Rao KA. Luteinizing Hormone in Controlled Ovarian Stimulation. Int J Infertil Fetal Med 2014; 5(3):75-86.
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