长方案促排卵中期添加黄体生成素对助孕结局的影响

目的:探讨GnRHa长方案促排卵中期LH水平为0.5～ 1.5 IU/L的患者外源性LH添加与否对其助孕结局的影响。方法:回顾性分析首次接受体外受精(IVF)或卵胞质内单精子注射(ICSI)助孕治疗、采用经典长方案、单用rFSH促排卵且在卵泡晚期血清黄体生成素(LH)水平在0.5～ 1.5 IU/L之间的患者199例,根据是否添加LH的情况分为3组,A组无添加(n=64),B组添加hMG(n=83),C组添加rLH(n=52)。分析3组对象的临床结局。结果:3组患者促排中期E2水平两两比较,A组>B组>C组,组间差异具有统计学意义(P<0.01);hCG注射日E2水平两两比较,B组>C组>A组,组间差异具有统计学意义(P=0.00);LH水平两两比较,C组>B组>A组,组间差异具有统计学意义(P=0.00);3组受精率分别为87.6%、68.4%和76.4%,差异有统计学意义(P=0.000);正常受精率分别为75.4%、62.1%和68.6%,组间具有显著差异(P=0.00);取消移植率分别为0.0%、14.5%和11.5%,差异显著(P<0.05)。3组间促性腺激素(Gn)使用天数、Gn使用总量、获卵数、成熟卵子数、优质胚胎率以及其他妊娠结局相关指标均无统计学差异(P>0.05)。结论:长方案促排卵中期LH水平在0.5～ 1.5 IU/L范围之间时无需添加外源性LH制剂,若添加外源性LH(包括hMG、rLH)会降低受精率以及正常受精率,增加移植取消率及OHSS发生率的风险。     

卵泡刺激素与高纯度尿促性腺激素联合方案在体外受精中有效性的评价

在控制性促排卵(controlled ovarian stimulation,COS)中,促卵泡生成素(FSH)联合高纯度尿促性腺激素(HP-hMG)促排卵的理论基础是基于促黄体生成素(LH)具有协同FSH促进卵泡发育和卵子成熟的作用。COS通常采用促性腺激素释放激素激动剂(GnRH-a)或促性腺激素释放激素抑制剂(GnRH-A)抑制早发内源性LH峰,致内源性LH水平降低,尤其在卵泡发育中晚期随着颗粒细胞上LH受体增加,对生理性LH的需求也增加。因此,理论上COS中FSH促排卵同时配伍一定量的LH活性制剂(如:HP-hMG,商品名为贺美奇)可能有利于改善COS结局。但目前FSH联合hMG应用的报道并不多,从目前有限的数据显示FSH联合hMG的多样化配伍方案均可获得满意的临床结果,关键是需要针对每个个体制定个体化的COS方案。     

卵巢储备正常者COH不同阶段添加高纯度人绝经期促性腺激素对IVF-ET结局的影响

目的:探讨卵巢储备正常者在促排卵不同阶段添加高纯度人绝经期促性腺激素(highly purified human menopausal gonadotrophin,HP-h MG)对体外受精-胚胎移植(IVF-ET)结局的影响。方法:收集接受IVF或单精子胞质内显微注射技术(ICSI)治疗的25~35岁卵巢储备功能正常的患者(n=153),根据是否添加HP-h MG及添加时机分为A组(未添加HP-h MG),B组(Gn第1日添加HP-h MG)和C组(Gn第6~8日添加HP-h MG),分析三组妊娠结局。结果:A组h CG注射日LH、E_2水平低于B组及C组(P0.05),A组h CG注射日P水平高于B组及C组(P0.05),获卵数及M_Ⅱ卵子数A组及C组高于B组(P0.05),优质胚胎率B组高于A组及C组(P0.05),累积妊娠率,C组(85%)高于A组(59.3%)及B组(67.6%),差异有统计学意义(P0.05),3组受精率、成熟卵率、种植率差异无统计学意义(P0.05)。结论:卵巢储备功能正常者在采用标准长方案促排卵时,中晚期添加HP-h MG可改善累积妊娠结局;卵泡发育不同阶段添加HP-h MG,可能适用于不同的人群。     

控制性超促排卵过程中血清LH低于正常时添加rLH或hMG的效果比较

目的:比较控制性超促排卵(COH)过程中血清促黄体生成素(LH)低于正常时添加基因重组LH(rLH)或人绝经期尿促性腺激素(hMG)的效果。方法:选取因输卵管因素不孕行常规IVF-ET患者85例,全部采用长方案超促排卵,均给予基因重组促卵泡激素(rFSH)进行超促排卵,超促排卵第6日时如血清LH≥1.2 mIU/ml,继续用rFSH,作为对照组(rFSH组,n=37);如血清LH<1.2 mIU/ml,则随机纳入到hMG组(rFSH+hMG,n=30)或rLH组(rFSH+rLH,n=18)。结果:3组间在促性腺激素(Gn)用量、COH天数、获卵数、双原核率、优质胚胎率、临床妊娠率方面均无统计学差异。hMG组的rFSH用量显著低于rLH组(P<0.01)。结论:在黄体期降调节长方案超促排卵第6日,如血清LH<1.2 mIU/ml时,添加hMG或rLH,可获得与对照组(rFSH组)相似的临床结果。与添加rLH组相比,添加hMG组降低了rFSH用量,减少了患者的费用。     

长方案卵泡中/后期添加含活性LH的不同促性腺激素制剂的临床结局比较

目的:探索经典长方案卵泡中/后期添加含活性黄体生成素(LH)的不同促性腺激素(Gn)制剂后行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)的最佳用药方案。方法:回顾性分析采用长方案行IVF/ICSI的1 441个周期患者的临床资料,根据中/后期所添加的Gn制剂不同,分为3组,A组为重组LH(r-LH)组,B组为人绝经期促性腺激素(h MG)组,C组为高纯h MG(HP-h MG)组。比较3组患者的Gn使用总量、Gn使用天数、获卵数、优质胚胎数、顶级优质胚胎数、临床妊娠率、活产率、早期流产率等。结果:C组Gn使用天数显著低于A组及B组,B组Gn使用总量显著高于A组及C组,A组和C组双原核(2PN)数、卵裂数、优质胚胎数、可利用胚胎数显著高于B组(P0.05),但A组与C组比较无统计学差异(P0.05);C组的顶级优质胚胎数高于A组及B组,差异有统计学意义(P0.05)。种植率A组为44.0%,B组为38.2%,C组为42.5%,各组间无统计学差异(P0.05)。临床妊娠率和活产率A组为62.5%和50.6%,B组为59.8%和44.0%,C组为65.3%和52.3%,A组和C组高于B组,但各组间比较无统计学差异(P0.05);早期流产率各组间相似。结论:长方案卵泡中后期添加LH制剂可获得较好的临床结局,但添加HP-h MG与r-LH可以减少Gn使用天数和总量,增加顶级优质胚胎数,临床妊娠率和活产率有增高的趋势,总体临床结局均优于国产h MG。     

长方案超促排卵过程中LH变化趋势对IVF/ICSI-ET结局的影响

目的:探讨控制性超促排卵(COH)周期中LH变化趋势对体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)结局的影响。方法:回顾性分析228个IVF/ICSI长方案周期,1按h CG注射日与降调节后Gn启动前血清LH水平的变化趋势,分为降低趋势组和升高趋势组;2将升高趋势组及降低趋势组根据COH中期与降调节后LH水平变化趋势分为A组和B组(升高趋势中的降低组和升高组),C组和D组(降低趋势中的降低组和升高组);3按照LH降低幅度将A组和C组分为A1组(下降幅度50%)和A2组(下降幅度≥50%)、C1组(下降幅度50%)和C2组(下降幅度≥50%),比较各组IVF/ICS-ET结局的差异。结果:1降低趋势组与升高趋势组获卵数、胚胎数、总的受精率、卵裂率、可利用胚胎率、优质胚胎率比较,差异均无统计学意义(P0.05),而胚胎种植率(26.09%vs 35.22%,P0.05)、临床妊娠率(45.11%vs 58.67%,P0.05)显著较升高趋势组低,早期流产率较升高组略高(26.08%vs 15.91%),但差异无统计学意义(P0.05)。2A组与B组、C组与D组相比较IVF/ICSI结局均无统计学差异。3 A1组、A2组的受精率、临床妊娠率、胚胎种植率、可利用胚胎率组间比较,差异均无统计学意义,但优质胚胎率A1组较高(65.48%vs40.68%,P0.05);C1组、C2组IVF/ICSI结局相比无统计学差异。结论:IVF/ICSI-ET长方案,h CG注射日较Gn启动前血清LH升高,有助于提高胚胎种植率、临床妊娠率,且在COH中期LH下降幅度50%,能显著提高优质胚胎率。故在COH的过程中适时添加LH,选择合适的血清LH水平启动COH,有助于改善助孕结局。     

应用拮抗剂及注射用尿促性素对正常反应患者体外受精-胚胎移植结局的影响

目的 探讨正常反应患者应用拮抗剂方案添加拮抗剂同时添加注射用尿促性素(HMG)的体外受精-胚胎移植(IVF-ET)结局。方法 本研究将2020年1月至2021年10月正常反应患者320在本中心行拮抗剂方案助孕,按照随机数字表法分为对照组168例和研究组152例。研究组在添加拮抗剂的同时添加HMG37.5～75 IU,对照组不添加HMG,对两组的IVF结局等进行前瞻性对照研究。结果 研究组较对照组HCG注射日雌二醇(E₂)、获卵数、受精率、D₃可用胚胎数、D₃优胚数、着床率、临床妊娠率增加,比较差异具有统计学意义(P<0.05)。结论 在正常反应患者中应用拮抗剂方案,添加思则凯同时添加HMG可改善体外受精-胚胎移植的结局。     

克罗米芬联合尿促性素对多囊卵巢综合征患者促排卵的临床效果

目的 探究多囊卵巢综合征（PCOS）患者采取克罗米芬联合尿促性素治疗对其促排卵的临床效果。方法 选取80例PCOS患者,采取随机数字表法分为对照组与试验组,每组40例。对照组采用克罗米芬治疗,试验组采用克罗米芬联合尿促性素治疗。比较两组促排卵效果、排卵率及妊娠率。结果 治疗前,两组患者排卵数、优势卵泡数、优势卵泡平均直径及卵泡成熟日比较,差异无统计学意义（P>0.05）。治疗后,两组患者排卵数、优势卵泡数均多于治疗前,卵泡成熟日短于治疗前,差异有统计学意义（P<0.05）,优势卵泡平均直径治疗前、治疗后比较,差异无统计学意义（P>0.05）。治疗后,试验组排卵数、优势卵泡数均多于对照组,差异有统计学意义（P<0.05）,试验组优势卵泡平均直径、卵泡成熟日与对照组比较,差异无统计学意义（P>0.05）。试验组患者排卵率82.50%、妊娠率55.00%均高于对照组的60.00%、32.50%,差异有统计学意义（P<0.05）。结论 克罗米芬联合尿促性素治疗PCOS患者可提高患者促排卵效果,提升排卵率及妊娠率,临床应用价值高。     

促排卵启动时间对子宫内膜异位症妇女体外受精妊娠结局的影响

目的探讨改良超长方案中根据降调节后的血清E_2水平选择合适的促性腺激素(Gn)启动时间在子宫内膜异位症(EMS)妇女体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)的临床应用。方法对98例IVF/ICSI-ET周期进行回顾性分析,改良超长方案治疗的65例为实验组,根据不孕因素分为A组(EMS性不孕)和B组(非EMS性不孕),A、B组均根据血清E_2水平选择恰当的时机启动Gn;另外行常规超长方案治疗的33例为对照组(C组,EMS性不孕),比较各组临床指标的差异。结果 (1)A组Gn使用总量[(2 330.4±747.8)IU]明显小于B组[(3 338.7±1 341.5)IU](P0.05),A组的受精率(77.6%)明显高于B组(65.8%)(P0.05),获卵数、妊娠率有增加趋势,但无统计学差异(P0.05)。(2)A组Gn起始剂量[(192.0±35.3)IU]、使用总量[(2 330.4±747.8)IU]均显著低于C组[(228.8±48.9)IU,(2 828.5±1 129.0)IU](P0.05),A组的启动时间[(35.9±7.4)d]明显大于C组[(28.0±0.0)d](P0.05),A组获卵数(8.8±4.7)也显著高于C组(6.1±3.9)(P0.05),两组的受精率、优质胚胎率、妊娠率均无统计学差异(P0.05)。结论在改良超长方案中,通过监测降调节后的血清E_2水平,选择恰当的时机启动Gn,可以在不影响结果的情况下减少Gn的用量,特别对于EMS患者更明显,是一种经济有效的降调节方案。     

高龄非输卵管性不孕妇女不同助孕方案妊娠结局的比较

目的为高龄非输卵管性不孕女性推荐更合理的助孕方案。方法选择行宫腔内人工授精(intrauterine insemination,IUI)和体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)的1 312名高龄输卵管通畅不孕女性(年龄≥35岁患者)共2 094个周期进行回顾性分析,其中IUI组827个周期,IVF组启动周期1 267个,移植周期798个。根据患者的年龄层次分为35~37岁,38~39岁和≥40岁3组,回顾性分析各组的临床资料和助孕结局。结果 3个不同年龄层的IUI组临床妊娠率分别为10.78%、8.72%和4.14%,IVF-ET组的移植周期临床妊娠率分别为53.03%、47.51%和22.69%,IUI和IVF组内及组间各年龄层临床妊娠率比较,差异有统计学意义(P0.05)。结论随着患者年龄的增加,IUI和IVF两种助孕方案的临床妊娠率均明显降低,建议年龄≥40岁输卵管通畅的不孕女性应积极行IVF治疗。     

Supplementation with human menopausal gonadotropin in the gonadotropin-releasing hormone antagonist cycles of women with high AMH: Pregnancy outcomes and serial hormone levels

ObjectiveTo evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH.Materials and methodsThis retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated.ResultsWe observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance.ConclusionsHMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.     

Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal,high, and poor responders to hMG

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropin-induced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P<0.001) prolonged, and the number of follicles and oocytes collected (5.7±0.7 vs 3.1±0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P<0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patient's own basal response. No improvement in response was expected in poor responders.     

Advantages of recombinant follicle-stimulating hormone over human menopausal gonadotropin for ovarian stimulation in intrauterine insemination: a randomized clinical trial in unexplained infertility

Objective

To compare two different gonadotropin preparations, human menopausal gonadotropin (hMG) and recombinant follicle-stimulating hormone (rFSH), combined with clomiphene citrate (CC) in women with unexplained infertility undergoing intrauterine insemination (IUI).

Study design

In this prospective clinical trial, couples prepared for IUI cycles were randomly allocated to two groups either to receive CC and hMG (group A, n = 127) or CC and rFSH (group B, n = 132) for ovarian stimulation. Outcomes including rates of clinical pregnancy, miscarriage, OHSS, multiple pregnancy, cancelation, and live birth were compared between groups.

Results

Duration of gonadotropin therapy was significantly shorter in group B (5.1 ± 0.84 vs. 4.7 ± 0.8 days, CI = 95%, P < 0.001). The total dose of administered gonadotropin was also significantly lower in group B (386.9 ± 68.2 vs. 348.2 ± 56.3 IU, CI = 95%, P < 0.001). Dominant follicle number (>17 mm), mean follicular diameter, and endometrial thickness on the day of hCG injection were similar. Clinical pregnancy, multiple pregnancies, abortion, live birth, ovarian hyperstimulation syndrome (OHSS), and cancelation rates were not statistically different between the groups.

Conclusion

IUI cycles in which rFSH had been administered may require shorter duration and a lower total gonadotropin dose.     

Effects of clomiphene citrate and leuprolide acetate on luteal-phase hyperprolactinemia during ovarian stimulation with menopausal gonadotropins

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation forin vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level >25 ng/ml, and 40% had mean luteal-phase prolactin levels >25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P=0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents lutealphase hyperprolactinemia in women undergoing ovarian stimulation with hMG.     

Comparative trial of clomiphene citrate/human menopausal gonadotropin and the contraceptive pill,followed by clomiphene citrate/human menopausal gonadotropin,in a gamete intrafallopian transfer program

Purpose It may sometimes be necessary to regulate cycles in assisted reproduction. Cycles can be regulated with gonadotropin releasing hormone (GnRHa) agonist but other methods can also be used. The aim of this study was to compare the pregnancy rate in a gamete intrafallopian transfer (GIFT) program in patients receiving a contraceptive pill/Clomid/human menopausal gonadotropin (hMG) regimen (study group), with the standard Clomid/hMG regime (control group). Fifty one patients in the study group were carefully matched for patient age, infertility diagnosis (female), semen parameters, number of follicles, and number of oocytes transferred into consideration with a control group.Results The overall pregnancy rate was 21.6% (11/51) in the study group and 47% (24/51) in the control group (P =0.01). However, the ongoing pregnancy rate in the two groups did not differ significantly, 11.8% (6/51) vs 27.5% (14/51) (P =0.08). In the study group, 7.8% of patients had to be seen over a weekend, compared to 13.7% in the control group (not significant). Conclusion From the findings we conclude that, although this method of controlling cycles can be useful in selected patients, it is not the ultimate method.     

多囊卵巢综合征患者在高孕激素超促排卵中LH与IVF/ICSI临床结局的相关性分析

目的:探讨在高孕激素超促排卵方案中基础血黄体生成素(LH)水平对多囊卵巢综合征(PCOS)患者行体外受精/卵胞质内单精子显微注射(IVF/ICSI)治疗的临床结局的影响。方法:回顾性分析183例PCOS患者采用从早卵泡期开始使用安宫黄体酮(MPA)联合促性腺激素(Gn)的高孕激素超促排卵方案行IVF/ICSI治疗;根据基础LH水平分为3组,A组:0~5 IU/L,B组:5~10 IU/L,C组:10 IU/L,分析3组患者在高孕激素超促排卵过程中不同血LH水平与控制性超促排卵特征及IVF临床结局的相关性。结果:3组在促排卵过程中LH水平均呈下降趋势,且在基础LH水平、中期LH水平、诱发排卵当日的LH水平及诱发排卵次日的LH水平3组间比较均有统计学差异(P0.05),在扳机日LH水平波动于0.08~12.33 IU/L之间,无一例发生自发性LH峰;在获卵数、成熟卵数及获卵率A组与C组间有统计学差异(P0.05),而成熟卵率、正常受精卵数、优质胚胎数及有效胚胎数3组间比较无统计学差异(P0.05);后续的冻融胚胎移植(frozen-thawed embryo transfer,FET)周期结果表明,临床妊娠率、早期流产率及继续妊娠率组间比较均无统计学差异(P0.05)。结论:高孕激素促排卵方案可有效预防PCOS患者行IVF/ICSI治疗的自发性LH峰发生,并且基础高LH水平未损害PCOS患者的卵子及胚胎质量,对其临床结局也无明显影响,因此高孕激素超促排卵方案是一种新的简单安全、高效的垂体非降调节超促排卵方案,但还需大样本多中心的随机对照试验进一步证实。     

黄体期使用生长激素在高龄卵巢储备功能减退患者中的临床应用

目的探讨黄体期使用生长激素(GH)对高龄卵巢储备功能减退(DOR)患者超促排卵治疗的影响。方法选择接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)且高龄(年龄≥35岁)DOR不孕患者156例为研究对象,均采用拮抗剂方案,分为研究组(加用GH)和对照组(不加用GH)。分析GH对促性腺激素(G n)使用总量、G n使用时间、获卵数、移植前内膜厚度、双原核(2 P N)率、优质胚胎率、着床率的影响。结果 Gn使用时间、Gn使用总量、移植前内膜厚度组间有统计学差异(P0.05)。h CG注射日E 2水平、获卵数、2 P N受精率、优质胚胎率、着床率、临床妊娠率及累积妊娠率组间无统计学差异(P0.05)。研究组临床妊娠率为28.0%、对照组为19.4%,研究组累积妊娠率为33.3%、对照组为20.0%,组间均无统计学差异(P0.05),但研究组临床妊娠率及累积妊娠率有上升趋势。结论 GH对年龄≥35岁DOR患者可明显降低Gn的使用总量及使用时间,增加子宫内膜的厚度,临床妊娠率及累积妊娠率有提高的趋势。