Long-acting FSH versus daily FSH for women undergoing assisted reproduction.
BACKGROUND
Assisted reproduction techniques (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) can help subfertile couples to create a family. It is necessary to induce multiple follicles; this is achieved by follicle stimulating hormone (FSH) injections. Current treatment regimens prescribe daily injections of FSH (urinary FSH with or without luteinizing hormone (LH) injections or recombinant FSH (rFSH)).Recombinant DNA technologies have produced a new recombinant molecule which is a long-acting FSH, named corifollitropin alfa (Elonva) or FSH-CTP. A single dose of long-acting FSH is able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week. The optimal dose of long-acting FSH is still being determined. A single injection of long-acting FSH can replace seven daily FSH injections during the first week of controlled ovarian stimulation (COS) and can make assisted reproduction more patient friendly.


OBJECTIVE
To compare the effectiveness of long-acting FSH versus daily FSH in terms of pregnancy and safety outcomes in women undergoing IVF or ICSI treatment cycles.


METHODS
We searched the following electronic databases, trial registers and websites: the Cochrane Central Register of Controlled Trials (CENTRAL), the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL, electronic trial registers for ongoing and registered trials, citation indexes, conference abstracts in the ISI Web of Knowledge, LILACS, Clinical Study Results (for clinical trial results of marketed pharmaceuticals), PubMed and OpenSIGLE (10 October 2011). We also carried out handsearches.


METHODS
All randomised controlled trials (RCTs) comparing long-acting FSH versus daily FSH in women who were part of a couple with subfertility and undertaking IVF or ICSI treatment cycles with a GnRH antagonist or agonist protocol were included.


METHODS
Data extraction and assessment of risk of bias was independently done by two review authors. Original trial authors were contacted in the case of missing data. We calculated Peto odds ratios for each outcome; our primary outcomes were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate.


RESULTS
We included four RCTs with a total of 2335 participants. A comparison of long-acting FSH versus daily FSH did not show evidence of difference in effect on overall live birth rate (Peto OR 0.92; 95% CI 0.76 to 1.10, 4 RCTs, 2335 women) or OHSS (Peto OR 1.12; 95% CI 0.79 to 1.60, 4 RCTs, 2335 women). We compared subgroups by dose of long-acting FSH. There was evidence of reduced live birth rate in women who received lower doses (60 to 120 μg) of long-acting FSH compared to daily FSH (Peto OR 0.60; 95% CI 0.40 to 0.91, 3 RCTs, 645 women). There was no evidence of effect on live births in the medium dose subgroup (Peto OR 1.03; 95% CI 0.84 to 1.27) and no evidence of effect on clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate, miscarriage rate or ectopic pregnancy rate.


CONCLUSIONS
The use of a medium dose of long-acting FSH is a safe treatment option and equally effective compared to daily FSH. Further research is needed to determine if long-acting FSH is safe and effective for use in hyper- or poor responders and in women with all causes of subfertility.
Faculty of Medical School, Radboud University Nijmegen, Nijmegen, Netherlands. a.pouwer@student.ru.nl.
Annefloor W
AW
Pouwer
Cindy
C
Farquhar
Jan A M
JA
Kremer
D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage*; D006728:Hormones / Q000008:administration & dosage*; D006801:Humans; D050498:Live Birth; D007986:Luteinizing Hormone / Q000008:administration & dosage*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D020554:Sperm Injections, Intracytoplasmic
D006728:Hormones; D011994:Recombinant Proteins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone