Clinical trial NCT00378001: Clinical Efficacy and Tolerability of Two FSH Preparations (Human FSH Versus rFSH - Follitropin Alpha) in Women Undergoing IVF
Official title: A Prospective, Multicenter, Investigator Blinded, Randomized, Concurrent Control Study of Efficacy and Tolerability of Two FSH Preparations (Fostimon® Versus Gonal-F®) in Women Undergoing IVF
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: Infertility, FSH, IVF, Ovarian stimulation
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
First posted: 2006-09-19
Enrollment: 152
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the clinical efficacy and general tolerability of two different subcutaneous FSH preparations (Fostimon®, IBSA vs Gonal-F®, Serono Inc.) when administered to patients undergoing controlled ovarian stimulation for IVF.

Detailed description: This is a prospective, multicenter, investigator blinded, randomized, concurrent control, phase III clinical trial. Patients meeting the eligibility requirements of the study will be randomly assigned to receive either the test drug (Fostimon®, IBSA) or the reference drug (Gonal-F®, Serono Inc.). Investigators will be blinded by not allowing them to have any contact with the study medications (supplied in boxes labeled in a manner that does not reveal the content of the boxes), and requesting that patients do not make any statements to the investigator that might indicate the treatment to which they were assigned. Equivalence testing with regard to the primary outcome variable will establish whether the two treatments are indeed similarly effective.

Eligibility criteria: Inclusion Criteria:

* \>/=18 and \<40 years old;

  * BMI between 18 and 30 kg/m2;
  * less than 3 previously completed IVF cycles (i.e. completed cycle = egg recovery);
  * basal FSH \<10 IU/L and E2 \<80 pg/mL;
  * Within 12 months of the beginning of the study, uterine cavity consistent with expected normal function as assessed through a hysterosalpingogram, sonohysterogram, or hysteroscopic examination;
  * \>10 antral follicles 2-10 mm in size;
  * Normal or clinically insignificant hematology and blood chemistry values. TSH levels must be within the normal limits for the testing laboratory, or the patient should be euthyroid as determined by the investigator (e.g. normal free thyroxine). TSH can be low secondary to exogenous thyroid medication where patient is euthyroid;
  * Able and willing to sign the Patient Consent Form and adhere to the study visitation schedule.

Exclusion Criteria:

* · age \<18 and \>/=40 years;

  * primary ovarian failure or women known as poor responders (i.e. requiring more than 300 IU of FSH as a starting dose in previous treatment cycles or having less than 3 oocytes retrieved, or with an E2 serum concentration \<1800 pmol/L/500pg/mL);
  * prior ovarian hyperstimulation syndrome (OHSS), polycystic ovarian syndrome that would normally be started at a lower FSH dose than is initially required by the study (i.e. 300 IU), or likely intolerance to even two days of 300 IU FSH.
  * one or both ovaries inaccessible for oocyte retrieval;
  * ovarian cysts \>20 mm;
  * hydrosalpinx that have not been surgically removed or ligated;
  * stage 3 or 4 endometriosis;
  * oocyte donation;
  * implantation of previously frozen embryos;
  * patients affected by pathologies associated with any contraindication of being pregnant;
  * hypersensitivity to the study medication;
  * abnormal bleeding of undetermined origin;
  * uncontrolled thyroid or adrenal dysfunction;
  * neoplasias;
  * severe impairment of renal and/or hepatic function;
  * use of concomitant medications that might interfere with study evaluations (e.g. nonstudy hormonal medications, prostaglandin inhibitors, psychotropic agents).

Primary outcomes:
measure: The primary endpoint is the total number of oocytes retrieved.
Secondary outcomes:
measure: Total FSH dose (IUs);number of days of FSH stimulation and stimulation duration;number of follicles >14 mm on the day of hCG injection;
measure: 17-β estradiol (E2) serum concentration on the day of hCG injection;cancellation rate with reasons;
measure: Fertilization rate: number of 2PN (or already cleaved) embryos;
measure: Total number of embryos,number transferred, frozen and discarded;implantation rate;number of transferred embryos; clinical pregnancy rate, per stimulated cycle, per oocyte retrieval and per embryo transfer.
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Fertility Physicians of Northern California
state: California
city: San Diego
country: United States
facility: San Diego Fertility Center
state: California
city: San Francisco
country: United States
facility: UCSF In Vitro Fertilization
state: California
city: Seattle
country: United States
facility: Seattle Reproductive Medicine
state: Washington
Study officials:
affiliation: Fertility Physicians of Northern California
name: Valerie Baker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSF In Vitro Fertilization
name: Victor Y Fujimoto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: San Diego Fertility Center
name: L. Michael Kettel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Reproductive Medicine
name: Michael R Soules, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med. 1998 Aug 27;339(9):573-7. doi: 10.1056/NEJM199808273390901.
citation: Porter RN, Smith W, Craft IL, Abdulwahid NA, Jacobs HS. Induction of ovulation for in-vitro fertilisation using buserelin and gonadotropins. Lancet. 1984 Dec 1;2(8414):1284-5. doi: 10.1016/s0140-6736(84)92840-x. No abstract available.
citation: Loumaye E. The control of endogenous secretion of LH by gonadotrophin-releasing hormone agonists during ovarian hyperstimulation for in-vitro fertilization and embryo transfer. Hum Reprod. 1990 May;5(4):357-76. doi: 10.1093/oxfordjournals.humrep.a137105. No abstract available.
citation: Hughes EG, Fedorkow DM, Daya S, Sagle MA, Van de Koppel P, Collins JA. The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials. Fertil Steril. 1992 Nov;58(5):888-96. doi: 10.1016/s0015-0282(16)55430-2.
citation: Smitz J, Devroey P, Braeckmans P, Camus M, Khan I, Staessen C, Van Waesberghe L, Wisanto A, Van Steirteghem AC. Management of failed cycles in an IVF/GIFT programme with the combination of a GnRH analogue and HMG. Hum Reprod. 1987 May;2(4):309-14. doi: 10.1093/oxfordjournals.humrep.a136540.
citation: Giudice E, Crisci C, Eshkol A, Papoian R. Composition of commercial gonadotrophin preparations extracted from human post-menopausal urine: characterization of non-gonadotrophin proteins. Hum Reprod. 1994 Dec;9(12):2291-9. doi: 10.1093/oxfordjournals.humrep.a138440.
citation: Howles CM, Loumaye E, Giroud D, Luyet G. Multiple follicular development and ovarian steroidogenesis following subcutaneous administration of a highly purified urinary FSH preparation in pituitary desensitized women undergoing IVF: a multicentre European phase III study. Hum Reprod. 1994 Mar;9(3):424-30. doi: 10.1093/oxfordjournals.humrep.a138522.
citation: Wikland M, Borg J, Hamberger L, Svalander P. Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction. Hum Reprod. 1994 Aug;9(8):1430-6. doi: 10.1093/oxfordjournals.humrep.a138724.
citation: Daya S, Gunby J, Hughes EG, Collins JA, Sagle MA. Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis. Fertil Steril. 1995 Aug;64(2):347-54.
citation: Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989 Jun;44(6):430-40. doi: 10.1097/00006254-198906000-00004. No abstract available.