The Utrogestan and hMG protocol in patients with polycystic ovarian syndrome undergoing controlled ovarian hyperstimulation during IVF/ICSI treatments

Xiuxian Zhu, Hongjuan Ye, Yonglun Fu, Xiuxian Zhu, Hongjuan Ye, Yonglun Fu

Abstract

Poor oocyte quality is a main concern for decreased reproductive outcomes in women with polycystic ovarian syndrome (PCOS) during controlled ovarian hyperstimulation (COH). A primary way to improve oocyte quality is to optimize the COH protocol. It was demonstrated that the viable embryo rate per oocyte retrieved in the Utrogestan and hMG protocol, a novel regimen based on frozen-thawed embryo transfer (FET), is statistically higher than that in the short protocol. Thus, a retrospective study was conducted to evaluate the endocrine characteristics and clinical outcomes in PCOS patients subjected to the Utrogestan and hMG protocol compared with those subjected to the short protocol.One hundred twenty three PCOS patients enrolled in the study group and were simultaneously administered Utrogestan and human menopausal gonadotropin (hMG) from cycle day 3 until the trigger day. When the dominant follicles matured, gonadotropin-releasing hormone agonist (GnRH-a) 0.1 mg was used as the trigger. A short protocol was applied in the control group including 77 PCOS women. Viable embryos were cryopreserved for later transfer in both groups. The primary outcome was the viable embryo rate per oocyte retrieved. The secondary outcomes included the number of oocytes retrieved, fertilization rate, and clinical pregnancy outcomes from FET cycles.The pituitary luteinizing hormone (LH) level was suppressed in most patients; however, the LH level in 13 women, whose basic LH level was more than 10 IU/L, surpassed 10 IU/L on menstruation cycle day (MC)9-11 and decreased subsequently. No significant between-group differences were observed in the number of oocytes retrieved (13.27 ± 7.46 vs 13.1 ± 7.98), number of viable embryos (5.57 ± 3.27 vs 5 ± 2.79), mature oocyte rate (90.14 ± 11.81% vs 93.02 ± 8.95%), and cleavage rate (97.69 ± 6.22% vs 95.89 ± 9.57%). The fertilization rate (76.11 ± 19.04% vs 69.34 ± 21.81%; P < 0.05), viable embryo rate per oocyte retrieved (39.85% vs 34.68%; P < 0.05), biochemical pregnancy rate (71.72% vs 56.67%; P < 0.05), clinical pregnancy rate (64.65% vs 51.65%; P < 0.05), and implantation rate (46.46% vs 31.35%; P < 0.05) in the study group were significant higher than those in the control group.This study shows that the Utrogestan and hMG protocol was feasible to improve the oocyte quality, possibly providing a new choice for PCOS patients undergoing IVF/ICSI treatments in combination with embryo cryopreservation.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flowchart of the study.
Figure 2
Figure 2
Serum hormone profiles present during ovarian stimulation in the 2 regimens. The red line refers to the Utrogestan + hMG group and the green line stands for the short-protocol group. The asterisk (∗) represents P < 0.05 at the time point.

References

    1. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
    1. Lauritsen MP, Bentzen JG, Pinborg A, et al. The prevalence of polycystic ovary syndrome in a normal population according to the Rotterdam criteria versus revised criteria including anti-Mullerian hormone. Hum Reprod 2014; 29:791–801.
    1. Li R, Zhang Q, Yang D, et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod 2013; 28:2562–2569.
    1. Lin H, Li Y, Li L, et al. Is a GnRH antagonist protocol better in PCOS patients? A meta-analysis of RCTs. PLoS One 2014; 9:e91796.
    1. Lainas TG, Sfontouris IA, Zorzovilis IZ, et al. Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT). Hum Reprod 2010; 25:683–689.
    1. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013; 6:1–13.
    1. Qiao J, Feng HL. Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence. Hum Reprod Update 2011; 17:17–33.
    1. Santos MA, Kuijk EW, Macklon NS. The impact of ovarian stimulation for IVF on the developing embryo. Reproduction 2010; 139:23–34.
    1. Huang X, Hao C, Shen X, et al. RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients. Reprod Biol Endocrinol 2013; 11:109–119.
    1. O’Neill KE, Senapati S, Dokras A. Use of gonadotropin-releasing hormone agonist trigger during in vitro fertilization is associated with similar endocrine profiles and oocyte measures in women with and without polycystic ovary syndrome. Fertil Steril 2015; 103:264–269.
    1. Zhu XX, Zhang XL, Fu YL. Utrogestan as an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. MEDICINE 2015; 94:e909.
    1. Zhu XX, Zhang XL, Fu YL. Effect of progesterone used to prevent LH surges in controlled ovarian stimulation. Reprod Contra 2015; 35:384–388.
    1. He W, Kuang YP. Effects of high serum LH level during mild ovarian stimulation protocol on IVF outcome of polycystic ovary syndrome patients: a matched case-control study. J Reprod Med 2014; 23:214–218.
    1. Ye Hong. Opinions about LH surge in controlled ovarian stimulation. J Repro Med 2010; 19:3–5.
    1. Jin Lei, Nie Rui. Premature LH surges and “rush harvesting”. J Repro Med 2010; 19:199–204.
    1. Allegra A, Marino A, Coffaro F, et al. GnRH antagonist-induced inhibition of the premature LH surge increases pregnancy rates in IUI-stimulated cycles. A prospective randomized trial. Hum Reprod 2007; 22:101–108.
    1. Lee TH, Lin YH, Seow KM, et al. Effectiveness of cetrorelix for the prevention of premature luteinizing hormone surge during controlled ovarian stimulation using letrozole and gonadotropins: a randomized trial. Fertil Steril 2008; 90:113–120.
    1. Hamdine O, Macklon NS, Eijkemans MJ, et al. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril 2014; 102:448–454.
    1. Xu B, Li Z, Zhang H, et al. Serum progesterone level effects on the outcome of in vitro fertilization in patients with different ovarian response: an analysis of more than 10,000 cycles. Fertil Steril 2012; 97:1321–1327.
    1. Huang CC, Lien YR, Chen HF, et al. The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles. Hum Reprod 2012; 27:2036–2045.
    1. Messinis IE. Ovarian feedback, mechanism of action and possible clinical implications. Hum Reprod Update 2006; 12:557–571.
    1. Kummer NE, Weitzman VN, Benadiva CA, et al. In vitro fertilization outcomes in patients experiencing a premature rise in luteinizing hormone during a gonadotropin-releasing hormone antagonist cycle. Fertil Steril 2011; 95:2592–2594.
    1. de Lignières B1. Oral micronized progesterone. Clin Ther 1999; 21:41–60.
    1. Gielen S, Hoon B, IJpma A, et al. LH regulated gene expression in the ovary of PCOS women, a role for PEG3 and TCF21. Fertil Steril 2013; 100:361–1361.
    1. Themmen APN, Huhtaniemi IT. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr Rev 2000; 21:551–583.
    1. Liu N, Ma Y, Wang S, et al. Association of the genetic variants of luteinizing hormone, luteinizing hormone receptor and polycystic ovary syndrome. Reprod Biol Endocrinol 2012; 10:36.
    1. Erickson GF, Magoffin DA, Garzo VG, et al. Granulosa cells of polycystic ovaries: are they normal or abnormal? Hum Reprod 1992; 7:293–299.
    1. Doldi N, Gessi A, Destefani A, et al. Polycystic ovary syndrome: anomalies in progesterone production. Hum Reprod 1998; 13:290–293.
    1. Gilling-Smith C, Willis DS, Beard RW, et al. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab 1994; 79:1158–1165.
    1. Fiad TM, Cunningham SK, McKenna TJ. Role of progesterone deficiency in the development of luteinizing hormone and androgen abnormalities in polycystic ovary syndrome. Eur J Endocrinol 1996; 135:335–339.
    1. Zhang X, Armstrong DT. Effects of follicle-stimulating hormone and ovarian steroids during in vitro meiotic maturation on fertilization of rat oocytes. Gamete Res 1989; 23:267–277.
    1. Osborn JC, Moor RM, Crosby IM. Effect of alterations in follicular steroidogenesis on the nuclear and cytoplasmic maturation of ovine oocytes. J Embryol Exp Morphol 1986; 98:187–208.
    1. Zavareh S, Saberivand A, Salehnia M. The effect of progesterone on the in vitro maturation and developmental competence of mouse germinal vesicle oocytes. Int J Fertil Steril 2009; 3:21–28.
    1. Aparicio IM, Garcia-Herreros M, O'shea LC, et al. Expression, regulation, and function of progesterone receptors in bovine cumulus oocyte complexes during in vitro maturation. Biol Reprod 2011; 84:910–921.
    1. Clemente M, de La Fuente J, Fair T, et al. Progesterone and conceptus elongation in cattle: a direct effect on the embryo or an indirect effect via the endometrium? Reproduction 2009; 138:507–517.
    1. Salehnia M, Zavareh S. The effects of progesterone on oocyte maturation and embryo development. Int J Fertil Steril 2013; 7:74–81.
    1. Youssef MA, Al-Inany HG, Evers JL, et al. Intra-venous fluids for the prevention of severe ovarian hyperstimulation syndrome. Cochrane Database Syst Rev 2011; CD001302.
    1. Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment. Reprod Biol Endocrinol 2012; 10:32.
    1. Fu YL, Zhang XL, Wang Y, et al. Effect of 200IU hCG replacing hMG in the late follicular phrase of controlled ovarian stimulation for IVF cycle. Reprod Contra 2014; 34:105–109.
    1. Fu YL, Wang Y, Cai RF, et al. A pilot study on the effect of 1000 IU hCG inducing final follicular maturation in patients undergoing controlled ovarian stimulation. Reprod Contra 2011; 31:596–599.

Source: PubMed

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