Hum. Reprod. Advance Access published online on December 15, 2007
Human Reproduction, doi:10.1093/humrep/dem388
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Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation
1 Reproductive Medicine Unit, Department of Gynaecology and Obstetrics, Jean Verdier Hospital, University Paris XIII, France 2 Fertility Clinic, Department of Obstetrics and Gynaecology, University Hospital of Odense, 5000 Odense C, Denmark 3 Assisted Conception Service, Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow G31 2ER, UK 4 Assisted Conception Unit, Royal Infirmary of Edinburgh, Edinburgh, UK 5 Centre for Reproductive Biology, University of Edinburgh, UK 6 MerckSerono, Geneva, Switzerland 7 Independent, London, UK
8 Correspondence address. E-mail: r.fleming{at}udcf.gla.ac.uk
BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH is required for normal hormone production and normal oocyte and embryo development, but follicular responses to LH may depend upon the stage of development. Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist.
METHODS: We employed a multi-centre, prospective, randomized approach. Women (n = 146) were treated in a long course high-dose GnRH agonist (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris, 300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone assessments of responses were measured at the start of r-hLH treatment, on FSH stimulation Days 0 and 8 and at the time of HCG administration.
RESULTS: The LH treatment was associated with increased small antral follicles prior to FSH stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN) embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation (P = 0.002).
CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed a possible modest clinical benefit. The results support other recent work exploring up-regulated androgen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept.
Key words: recombinant human LH/androgen/follicle growth/controlled ovarian stimulation
Submitted on March 19, 2007; resubmitted on October 16, 2007; accepted on November 14, 2007.
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