title: A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology.
abstract: BACKGROUND
  Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice.
  
  
  METHODS
  A 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS).
  
  
  RESULTS
  In total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%).
  
  
  CONCLUSIONS
  In German routine clinical practice, the most common reasons for using the 2:1 formulation of follitropin alfa and lutropin alfa for women undergoing ART were POR, low baseline LH, and age. Severe OHSS incidence was low and similar to that reported previously.
authors.affiliation: Centre for Gynaecology, Endocrinology and Reproductive Medicine, Ulm and Stuttgart D-70174, Germany. buehler.kf@t-online.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bühler
authors.forename: Olaf G J
authors.initials: OG
authors.lastname: Naether
authors.forename: Wilma
authors.initials: W
authors.lastname: Bilger
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D055815:Young Adult; D002626:Chemistry, Pharmaceutical; D016208:Databases, Factual / Q000639:trends; D004359:Drug Therapy, Combination; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000737:chemistry; D015292:Glycoprotein Hormones, alpha Subunit / Q000008:administration & dosage / Q000737:chemistry; D007247:Infertility, Female / Q000188:drug therapy / Q000453:epidemiology; D018873:Pregnancy Rate / Q000639:trends; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000639:trends; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D027724:Reproductive Techniques, Assisted / Q000639:trends
chemical_list: D043373:Follicle Stimulating Hormone, Human; C571801:follitropin alfa; D015292:Glycoprotein Hormones, alpha Subunit; D011994:Recombinant Proteins