控制性促排卵晚卵泡期孕酮升高天数对临床结局的影响
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摘要
目的探讨促排卵过程中,晚卵泡期血清孕酮(P)升高天数对新鲜周期胚胎移植临床结局的影响。方法回顾性分析2011年1月至2018年9月在我院生殖中心行IVF-ET助孕治疗的2 423个周期的临床资料。根据晚卵泡期至扳机日P升高天数分为4组:A组(全程P均<3.17nmol/L,1 445个周期)、B组(P≥3.17nmol/L仅1d,734个周期)、C组(P≥3.17nmol/L共2d,223个周期)、D组(P≥3.17nmol/L共3d,21个周期)。比较4组间患者的IVF妊娠结局。再按不同促排卵方案分为短效长方案组、长效长方案组、超长方案组、改良方案组和卵泡期长方案组,比较同一促排卵方案下P升高持续天数对妊娠率的影响。结果 A组的受精率显著高于B、C组(P<0.05);A组的可用胚胎率显著高于C组(P<0.05);A、B、C三组间的优质胚胎率比较无显著性差异(P>0.05),但均显著高于D组(P<0.01)。A组的胚胎种植率最高,显著高于B、C、D组(P<0.01)。4组间的临床妊娠率、生化妊娠率比较均无显著性差异(P>0.05)。短效长方案中A组的临床妊娠率显著高于C组(P<0.01),B、C、D组间临床妊娠率比较无显著性差异(P>0.05)。4组中长效长方案、卵泡期长方案的临床妊娠率比较无显著性差异(P>0.05)。超长方案、改良方案中均没有血清P升高≥3d的患者,A、B、C组间的临床妊娠率比较无显著性差异(P>0.05)。HCG日P升高影响临床妊娠的最佳临界值约为2.93nmol/L,该点对应的敏感度为52.9%,特异度为43.0%。结论促排卵过程中,随着血清P≥3.17nmol/L天数的增加,虽然获卵数增加,但优质胚胎率、胚胎种植率有下降的趋势。HCG日P升高对临床妊娠有一定的预测作用。
Objective:To explore the effects of progesterone(P)elevated days in late follicular phase on the clinical outcome of fresh embryo transfer cycle.Methods:The data of 2 423 patients undergone IVF/ICSI in the Department of Reproductive Center,Jiangmen Central Hospital from January 2011 to September 2018 were retrospectively analyzed.According to the progesterone elevation days in late follicular phase before triggering,the patients were divided into four groups:group A:P<3.17 nmol/L(n=1 445);group B:P≥3.17 nmol/L for 1 day(n=734);group C:P≥3.17 nmol/L for 2 days(n=233);group D:P≥3.17 nmol/L for 3 days(n=21).The pregnancy outcomes of patients among the 4 groups were compared.Then the cycles were subdivided into shortacting long-term protocol group,long-acting long-term protocol group,super-long protocol group,modified protocol group and follicular phase long-term protocol group according to different ovulation induction regimen.Results:The fertilization rate of group A was significantly higher than that of group B and C(P<0.05).The available embryo rate of group A was significantly higher than that of group C(P<0.05).There was no significantly difference in the good quality embryos among the group A,B and C(P>0.05),but significantly higher than group D(P<0.05).The implantation rate of group A was the highest,which was significantly higher than that of group B,C and D(P<0.01).There was no significant difference in clinical pregnancy rate and biochemical pregnancy rate among the 4 groups(P>0.05).The clinical pregnancy rate of the short-acting longterm protocol in group A was significantly higher than that in group C(P<0.01).There was no significant difference in clinical pregnancy rate among group B,C and D(P>0.05).There was no significant difference in the clinical pregnancy rate among the long-acting long-term protocol and the follicular phase long-term protocol in the 4 groups(P>0.05).There were no serum P elevation≥3 days in the patients with ultra-long and modified protocol.There was no significant difference in clinical pregnancy rate among group A,B and C(P>0.05).The cut-off value of P on HCG day was 2.93 nmol/L.The corresponding sensitivity was 52.9%and the specificity was 43.0%.Conclusions:With the increase in days of P≥3.17 nmol/L during controlled ovarian stimulation,the number of oocytes retrieved was increased,but the high quality embryo rate and implantation rate were decreased significantly,suggesting that serum P elevation on HCG day may have a certain predictive effect on clinical pregnancy.
Objective:To explore the effects of progesterone(P)elevated days in late follicular phase on the clinical outcome of fresh embryo transfer cycle.Methods:The data of 2 423 patients undergone IVF/ICSI in the Department of Reproductive Center,Jiangmen Central Hospital from January 2011 to September 2018 were retrospectively analyzed.According to the progesterone elevation days in late follicular phase before triggering,the patients were divided into four groups:group A:P<3.17 nmol/L(n=1 445);group B:P≥3.17 nmol/L for 1 day(n=734);group C:P≥3.17 nmol/L for 2 days(n=233);group D:P≥3.17 nmol/L for 3 days(n=21).The pregnancy outcomes of patients among the 4 groups were compared.Then the cycles were subdivided into shortacting long-term protocol group,long-acting long-term protocol group,super-long protocol group,modified protocol group and follicular phase long-term protocol group according to different ovulation induction regimen.Results:The fertilization rate of group A was significantly higher than that of group B and C(P<0.05).The available embryo rate of group A was significantly higher than that of group C(P<0.05).There was no significantly difference in the good quality embryos among the group A,B and C(P>0.05),but significantly higher than group D(P<0.05).The implantation rate of group A was the highest,which was significantly higher than that of group B,C and D(P<0.01).There was no significant difference in clinical pregnancy rate and biochemical pregnancy rate among the 4 groups(P>0.05).The clinical pregnancy rate of the short-acting longterm protocol in group A was significantly higher than that in group C(P<0.01).There was no significant difference in clinical pregnancy rate among group B,C and D(P>0.05).There was no significant difference in the clinical pregnancy rate among the long-acting long-term protocol and the follicular phase long-term protocol in the 4 groups(P>0.05).There were no serum P elevation≥3 days in the patients with ultra-long and modified protocol.There was no significant difference in clinical pregnancy rate among group A,B and C(P>0.05).The cut-off value of P on HCG day was 2.93 nmol/L.The corresponding sensitivity was 52.9%and the specificity was 43.0%.Conclusions:With the increase in days of P≥3.17 nmol/L during controlled ovarian stimulation,the number of oocytes retrieved was increased,but the high quality embryo rate and implantation rate were decreased significantly,suggesting that serum P elevation on HCG day may have a certain predictive effect on clinical pregnancy.
引文
[1]Venetis CA,Kolibianakis EM,Bosdou JK,et al.Progesterone elevation and probability of pregnancy after IVF:a systematic review and meta-analysis of over 60 000cycles[J].Hum Reprod Update,2013,19:433-457.
[2]Bosch E,Labarta E,Crespo J,et al.Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization:analysis of over4000cycles[J].Hum Reprod,2010,25:2092-2100.
[3]Huang CC,Lien YR,Chen HF,et a1.The duration of pre-ovulatory serum progesterone elevation before hCG administration affectsthe outcome of IVF/ICSI cycles[J].Hum Reprod,2012,27:2036-2045.
[4]Melo MA,Meseguer M,Garrido N,et al.The significance of premature luteinization in an oocyte-donation programme[J].Hum Reprod,2006,21:1503-1507.
[5]Huang B,Ren X,Wu L,et al.Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles[J/OL].PLoS One,2016,11:e0145895.
[6]Vanni VS,Somigliana E,Reschini M,et al.Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles[J/OL].PLoS One,2017,12:e0176482.
[7]徐玉萍,曹云霞,丛林,等.人绒毛膜促性腺激素注射日血清孕酮水平对胚胎发育及体外受精-胚胎移植结局的影响[J].生殖医学杂志,2007,16:255-258.
[8]Salamonsen LA,Evans J,Nguyen HP,et al.The microenvironment of human implantation:determinant of reproductive success[J].Am J Reprod Immunol,2016,75:218-225.
[9]Nikas G,Develioglu OH,Toner JP,et al.Endometrial pinopodes indicate a shift in the window of receptivity in IVFcycles[J].Hum Reprod,1999,14:787-792.
[10]Labarta E,Martínez-Conejero JA,AlamáP,et al.Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase:a functional genomics analysis[J].Hum Reprod,2011,26:1813-1825.
[11]Haouzi D,Bissonnette L,Gala A,et a1.Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration[J].Biomed Res Int,2014,2014:951937.
[12]Lee VC,Li RH,Chai J,et a1.Effect of preovulatory progesterone elevation and duration of progesterone elevation on the pregnancy rate of frozen-thawed embryo transfer in natural cycles[J].Fertil Steril,2014,101:1288-1293.
[13]Werner MD,Forman EJ,Hong KH,et al.Defining the“sweet pot”for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone:an analysis of 10,280first in vitro fertilization cycles[J].Fertil Steril,2014,102:1312-1317.
[14]Lawrenz B,Long J,Stoop D,et al.Impact of stimulation duration and gonadotropin type on the incidence of premature progesterone elevation-a retrospective analysis of the Ensure data[J].Gynecol Endocrinol,2018,34:1044-1047.
[15]Wong KM,van Wely M,Mol F,et al.Fresh versus frozen embryo transfers in assisted reproduction[J].Cochrane Database Syst Rev,2017,3:CD011184.
[16]Shi Y,Sun Y,Hao C,et al.Transfer of fresh versus frozen embryos in ovulatory women[J].N Engl J Med,2018,378:126-136.
[17]Roque M,Valle M,Sampaio M,et al.Does freeze-all policy affect IVF outcomes in poor responders?[J].Ultrasound Obstet Gynecol,2018,52:530-534.
[2]Bosch E,Labarta E,Crespo J,et al.Circulating progesterone levels and ongoing pregnancy rates in controlled ovarian stimulation cycles for in vitro fertilization:analysis of over4000cycles[J].Hum Reprod,2010,25:2092-2100.
[3]Huang CC,Lien YR,Chen HF,et a1.The duration of pre-ovulatory serum progesterone elevation before hCG administration affectsthe outcome of IVF/ICSI cycles[J].Hum Reprod,2012,27:2036-2045.
[4]Melo MA,Meseguer M,Garrido N,et al.The significance of premature luteinization in an oocyte-donation programme[J].Hum Reprod,2006,21:1503-1507.
[5]Huang B,Ren X,Wu L,et al.Elevated progesterone levels on the day of oocyte maturation may affect top quality embryo IVF cycles[J/OL].PLoS One,2016,11:e0145895.
[6]Vanni VS,Somigliana E,Reschini M,et al.Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles[J/OL].PLoS One,2017,12:e0176482.
[7]徐玉萍,曹云霞,丛林,等.人绒毛膜促性腺激素注射日血清孕酮水平对胚胎发育及体外受精-胚胎移植结局的影响[J].生殖医学杂志,2007,16:255-258.
[8]Salamonsen LA,Evans J,Nguyen HP,et al.The microenvironment of human implantation:determinant of reproductive success[J].Am J Reprod Immunol,2016,75:218-225.
[9]Nikas G,Develioglu OH,Toner JP,et al.Endometrial pinopodes indicate a shift in the window of receptivity in IVFcycles[J].Hum Reprod,1999,14:787-792.
[10]Labarta E,Martínez-Conejero JA,AlamáP,et al.Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase:a functional genomics analysis[J].Hum Reprod,2011,26:1813-1825.
[11]Haouzi D,Bissonnette L,Gala A,et a1.Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration[J].Biomed Res Int,2014,2014:951937.
[12]Lee VC,Li RH,Chai J,et a1.Effect of preovulatory progesterone elevation and duration of progesterone elevation on the pregnancy rate of frozen-thawed embryo transfer in natural cycles[J].Fertil Steril,2014,101:1288-1293.
[13]Werner MD,Forman EJ,Hong KH,et al.Defining the“sweet pot”for administered luteinizing hormone-to-follicle-stimulating hormone gonadotropin ratios during ovarian stimulation to protect against a clinically significant late follicular increase in progesterone:an analysis of 10,280first in vitro fertilization cycles[J].Fertil Steril,2014,102:1312-1317.
[14]Lawrenz B,Long J,Stoop D,et al.Impact of stimulation duration and gonadotropin type on the incidence of premature progesterone elevation-a retrospective analysis of the Ensure data[J].Gynecol Endocrinol,2018,34:1044-1047.
[15]Wong KM,van Wely M,Mol F,et al.Fresh versus frozen embryo transfers in assisted reproduction[J].Cochrane Database Syst Rev,2017,3:CD011184.
[16]Shi Y,Sun Y,Hao C,et al.Transfer of fresh versus frozen embryos in ovulatory women[J].N Engl J Med,2018,378:126-136.
[17]Roque M,Valle M,Sampaio M,et al.Does freeze-all policy affect IVF outcomes in poor responders?[J].Ultrasound Obstet Gynecol,2018,52:530-534.