Recombinant human luteinizing hormone supplementation may improve embryo quality in in vitro fertilization/intracytoplasmic sperm injection cycles with gonadotropin-releasing hormone antagonist protocol

Amir Wiser, Ariel Hourvitz, Yoav Yinon, Jacob Levron, Jehoshua Dor, Shai Elizur
DOI: 10.4236/ojog.2011.12007                

Abstract

Objective: To evaluate the effects of recombinant LH (rLH) supplementation on embryo quality in IVF/ICSI cycles with GnRH antagonist. Study design: Prospective, randomized controlled study. Thirty women were enrolled, 15 in the study (FSH + rLH) group and 15 in the control (rFSH only) group. On the day GnRH antagonist was started, the study group patients received 75 IU of rLH in addition to rFSH. The main outcome measures were embryo quality, number of oocytes retrieved, and fertilization rate. Results: The rLH group had significantly more top-quality embryos (36/43, 84%) compared to the control group (40/68, 59%; p = 0.006). Fertilization rates and number of oocytes retrieved were similar between groups. Progesterone and estradiol (E2) concentrations in follicular fluid were higher in the study group compared to controls (16.5 ± 2.5 µg/ml vs. 11.4 ± 3.6 µg/ml progesterone, P = 0.07; and 687 ± 112 pg/ml vs. 471 ± 65 pg/ml E2, p = 0.08). Conclusion: Adding rLH to ovarian stimulation with GnRH antagonist can yield higher quality embryos.

Keywords

Recombinants LH; Antagonist Protocol; Embryo Quality; IVF Treatment

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Weghofer, A., Munné, S., Brannath, W., Chen, S., Tomkin, G., Cekleniak, N., et al. (2008) The impact of LH-containing gonadotropins on diploidy rates in preimplantation embryos: Long protocol stimulation. Human Reproduction, 23, 499-503. doi:10.1093/humrep/dem412
[2]	Manna, C., Rahman, A., Sbracia, M., Pappalardo, S., Mohamed, E.I., Linder, R., et al. (2005) Serum luteinizing hormone, follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction. Gynecological Endocrinology, 20, 188-194. doi:10.1080/09513590400027141
[3]	Albano, C., Smitz, J., Camus, M., Riethmüller-Winzen H, Van Steirteghem A and Devroey P. (1997) Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation. Fertility and Sterility, 6, 917-922. doi:10.1016/S0015-0282(97)81407-0
[4]	Kolibianakis, E.M., Venetis, C.A. and Tarlatzis, B.C. (2009) Role of the endocrine profile for the achievement of pregnancy with IVF. Reproductive BioMedicine Online, 18, 37-43. doi:10.1016/S1472-6483(10)60447-6
[5]	Ziebe, S., Lundin, K., Janssens, R., Helmgaard, L. and Arce, J.C. (2007) MERIT (Menotrophin vs Recombinant FSH in vitro Fertilisation Trial) Group. Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF. Human Reproduction, 22, 2404-2413. doi:10.1093/humrep/dem221
[6]	Acevedo, B., Sanchez, M., Gomez, J.L., Cuadros, J., Ricciarelli, E. and Hernández, E.R. (2004) Luteinizing hormone supplementation increases pregnancy rates in gonadotropin-releasing hormone antagonist donor cycles. Fertility and Sterility, 82, 343-347. doi:10.1016/j.fertnstert.2004.03.020
[7]	Cédrin-Durnerin, I., Grange-Dujardin, D., Laffy, A., Parneix, I., Massin, N., Galey, J., et al. (2004) Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: A prospective randomized study. Human Reproduction, 19, 1979-1984. doi:10.1093/humrep/deh369
[8]	Durnerin, C.I., Erb, K., Fleming, R., Hillier, H., Hillier, S.G., Howles, C.M., et al. (2008) Luveris Pretreatment Group. Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation. Human Reproduction, 23, 421-426. doi:10.1093/humrep/dem388
[9]	McNatty, K.P., Smith, D.M., Makris, A., Osathanondh, R. and Ryan, K.J. (1979) The microenvironment of the human antral follicle: Interrelationships among the steroid levels in antral fluid, the population of granulosa cells, and the status of the oocyte in vivo and in vitro. The Journal of Clinical Endocrinology & Metabolism, 49, 851-860. doi:10.1210/jcem-49-6-851
[10]	Hompes, P.G., Broekmans, F.J., Hoozemans, D.A. and Schats. R. (2008) FIRM group. Effectiveness of highly purified human menopausal gonadotropin vs. recombinant follicle-stimulating hormone in first-cycle in vitro fertilization-intracytoplasmic sperm injection patients. Fertility and Sterility, 89, 1685-1693. doi:10.1016/j.fertnstert.2007.05.039
[11]	Andersen, A.N., Devroey, P. and Arce, J.C. (2006) Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: A randomized assessor-blind controlled trial. Human Reproduction, 21, 3217-3227. doi:10.1093/humrep/del284
[12]	McKenzie, L.J., Pangas, S.A., Carson, S.A., Kovanci, E., Cisneros, P., Buster, J.E., Amato, P. and Matzuk, M.M. (2004) Human cumulus granulosa cell gene expression: A predictor of fertilization and embryo selection in women undergoing IVF. Human Reproduction, 19, 2869-2874. doi:10.1093/humrep/deh535
[13]	Hassan, H.A. (2001) Cumulus cell contribution to cytoplasmic maturation and oocyte developmental competence in vitro. Journal of Assisted Reproduction and Genetics, 18, 539-543.
[14]	Assou, S., Anahory, T., Pantesco, V., Le Carrour, T., Pellestor, F., Klein, B., et al. (2006) The human cumulus—Oocyte complex gene-expression profile. Human Reproduction, 21, 1705-1719. doi:10.1093/humrep/del065
[15]	Platteau, P., Smitz, J., Albano, C., S?rensen, P., Arce, J.C. and Devroey, P. (2004) Exogenous luteinizing hormone activity may influence the treatment outcome in in vitro fertilization but not in intracytoplasmic sperm injection cycles. Fertility and Sterility, 81, 1401-1404. doi:10.1016/j.fertnstert.2003.09.077
[16]	Lossl, K., Andersen, A.N., Loft, A., Freiesleben, N.L., Bangsb?ll, S. and Andersen, C.Y. (2006) Androgen priming using aromatase inhibitor and hCG during early-follicular-phase GnRH antagonist down-regulation in modified antagonist protocols. Human Reproduction, 21, 2593-2600. doi:10.1093/humrep/del221
[17]	Bosch, E., Vidal, C., Labarta, E., Simon, C., Remohi, J. and Pellicer, A. (2008) Highly purified hMG versus recombinant FSH in ovarian hyperstimulation with GnRH antagonists—A randomized study. Human Reproduction, 23, 2346-2351. doi:10.1093/humrep/den220
[18]	MERIT* Group. (2007) Endocrine profile in serum and follicular fluid differs after ovarian stimulation with HP-hMG or recombinant FSH in IVF patients. Human Reproduction, 22, 676-687.
[19]	Couse, J.F., Hewitt, S.C., Bunch, D.O., Sar, M., Walker, V.R., Davis, B.J., et al. (1999) Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science, 17, 2328-2331.
[20]	Niu, Z., Feng, Y., Zhang, A., Sun, Y. and Zhang, H. (2008) Progesterone levels on oocyte retrieval day can predict the quantity of viable embryos but not pregnancy outcome of intracytoplasmic sperm injection. Gynecological Endocrinology, 24, 452-458. doi:10.1080/09513590802196247