A Comparison of Recombinant Follicule Stimulating Hormone (REC FSH) To Combination REC FSH Plus Human Menopausal Gonadotropin (HMG) in Gonadotropin Releasing Hormone (GNRH) Antagonist in Vitro Fertilization (IVF) Cycles

Abstract

To evaluate the clinical outcomes of adding LH, as hMG, in GnRH antagonist protocols in younger versus older patients. Retrospective analysis comparing all patients undergoing assisted reproduction treated during 2001 through 2003 with GnRH antagonist protocols in a large group practice with a single IVF laboratory. A total of more than 1300 fresh, nondonor IVF cycles were available for analysis. These included a broad spectrum of patients presenting for assisted reproductive technologies. Protocols using a GnRH antagonist (Cextrorelix®, Serono, Inc., Rockland, MA or Ganarelix®, Organon, West Orange, NJ), were employed along with the administration of rec FSH (Follitropin-α, Serono or Follitropin-β, Organon) or rec FSH supplemented with hMG (Pergonal®, Serono or Repronex®, Ferring, Suffren, NY) in a large cohort of younger (<35 years old) versus older (≥35 years old) patients. Final follicular maturation was achieved with either urinary (10,000 IU im) or recombinant hCG (250 ug sc Ovidrel®, Serono) when 2 or more lead follicles had a minimum mean diameter of 20 mm. Oocyte retrieval was performed 35 hours after hCG injection. Standard laboratory protocols were followed, including intracytoplasmic sperm injection, assisted hatching for cleavage embryos, and extended culture for blastocyst transfer, as clinically appropriate. Ultrasound guided embryo transfer was performed and all patients received luteal progesterone support. Serum hCG levels were measured 15 days after retrieval, and a clinical pregnancy was defined as the presence of a gestational sac on ultrasound. The main outcome measures were oocytes retrieved and pregnancy rates for patients treated with rec FSH alone versus rec FSH plus hMG. Data were analyzed by multiple linear or logistic regression depending on type. A p<0.05 was considered statistically significant. As expected, fertility declined with age as assessed by multiple response variables (p < 0.0001). Patients treated with rec FSH alone had significantly more oocytes retrieved (+2.1, see Figure), mature oocytes (+2.2), oocytes fertilized (+1.9), embryos that cleaved (+1.5) and 6-cell embryos at day 3 of culture (+0.5) compared to patients treated with rec FSH+hMG. Rec FSH treatment yielded more oocytes, better embryo development and tended to increase pregnancy rates compared to treatment with rec FSH in combination with hMG. Although both FSH and LH are obligatory for follicular development in humans, exogenous hMG does not appear to be required or beneficial in most IVF patients given GnRH antagonists to block endogenous LH surges.