依据扳机日血清E2值制定HCG剂量对ICSI结局的影响

目的 探讨依据扳机日血清E2值制定HCG剂量对卵胞浆内单精子注射（ICSI）促排卵结局的影响。方法 前瞻性分析2012年1－12月在上海瑞金医院生殖中心行ICSI助孕依据HCG日血清E2值制定不同HCG扳机剂量的117名患者的促排卵结局。HCG扳机剂量制定原则：E2值≤16 515 pmol/L为7000 IU、E2值介于16 516～23 854 pmol/L为5000 IU、E2值≥23 855 pmol/L为3000 IU。结果 3组MⅡ率、受精率的差异无统计学意义。7000 IU组卵裂率低于5000 IU组（96.43% vs. 99.62%）,差异有统计学意义（P<0.05）,7000 IU组可用胚胎率高于3000 IU组和5000 IU组（65.43% vs.55.69%和57.74%）,差异有统计学意义（P<0.05）。5000 IU组发生1例中度OHSS。3组新鲜移植周期的平均移植胚胎数、临床妊娠率和胚胎着床率的差异无统计学意义。结论 依据HCG日E2值制定HCG扳机剂量不影响卵母细胞成熟率和妊娠率,即高E2值予以低剂量HCG,低E2值予以高剂量HCG的原则是可行的。     

人工授精周期中诱发排卵方法选择

在人工授精周期促排卵治疗时,为了减少卵巢的过度刺激,降低多胎妊娠发生率,必须进行卵巢微刺激的控制性促排卵方案,主要通过控制早卵泡期的启动数及优势卵泡的排卵数来完成。氯米芬、来曲唑是一线方案,人绝经期促性腺激素（HMG）或卵泡刺激素（FSH）低剂量渐增方案是比较容易达到控制目的的方案。在促排卵周期中,监测自发性黄体生成激素（LH）峰形成后产生的级联效应,可以获得最佳妊娠率。注射人绒毛膜促性腺激素（HCG）扳机后36h完成人工授精手术可能是最佳时机。     

小剂量地塞米松片对IVF/ICSI-ET促排卵过程中孕酮水平及助孕结局的影响

目的:探讨小剂量地塞米松片对体外受精/卵细胞浆内单精子注射-胚胎移植（IVF/ICSI-ET）促排卵过程中孕酮水平和助孕结局的影响。方法:选择2014年1月1日至2017年12月31日于西南医科大学附属医院行IVF/ICSI-ET助孕的不孕症患者进行回顾性分析,其中促排卵过程中非扳机日孕酮≥3.18 nmol/L的IVF/ICSI-ET患者567例,均常规促排卵,实验组（221例）加用地塞米松片0.75 mg/d口服直至扳机日,对照组（346例）仅常规促排卵。比较两组患者孕酮水平的变化,以及成熟卵率、优质胚胎率的差异;分析使用地塞米松片不同天数对助孕结局的影响。结果:实验组扳机日孕酮水平及因扳机日高孕酮取消移植率显著低于对照组（P<0.05）;使用地塞米松片1～2天、3～4天、≥5天的胚胎种植率、临床妊娠率、活产率差异无统计学意义（P>0.05）。结论:IVF/ICSI-ET促排卵过程中,地塞米松片应用于非扳机日孕酮水平≥3.18 nmol/L的患者可降低扳机日孕酮水平及周期取消率。     

促排卵周期中的黄体支持

促排卵治疗是不孕症治疗过程中常见的治疗手段,亦是辅助生殖技术的重要环节,促排卵治疗后导致的黄体功能不全及对子宫内膜功能的影响,导致胚胎着床失败,妊娠率下降。临床研究提示黄体支持有助于改善促排卵周期的妊娠结局。目前尚无公认的最佳黄体支持方案,黄体支持的药物主要包括人绒毛膜促性腺激素（HCG）、黄体酮、雌激素及促性腺激素释放激素激动剂（GnRH-a）。药物使用的种类、剂型和使用时间无统一标准。     

影响人工授精妊娠率的多因素分析

目的:探讨影响夫精人工授精妊娠率的相关因素。方法:选取2013年3月至2014年9月在南通大学附属医院生殖医学中心行宫腔内人工授精(IUI)治疗的夫妇146对,共277个周期。分析女性年龄、不孕年限、IUI治疗周期数、促排卵方案,扳机方法及扳机日相关指标等与临床妊娠率的关系。结果:年龄25岁组的妊娠率明显高于年龄30岁组(25.8%vs 11.2%,P0.05);妊娠组的扳机日促黄体生成素(LH)水平高于非孕组[(29.7±8.44)vs(16.6±1.52),P0.05]。子宫内膜分型为A型者的妊娠率显著高于非A型者(P0.05)。GnRH-a扳机后排卵率优于HCG(P0.05);4个治疗周期内随着周期数的增加累计妊娠率上升,卵泡期为10~16天妊娠率最高。结论:夫精人工授精治疗中,患者年龄、HCG日LH值、子宫内膜分型与妊娠率相关,GnRH-a扳机后排卵率优于HCG。     

GnRH-a联合低剂量HCG诱发卵母细胞成熟在行PGD/PGS助孕患者中的应用

目的:探讨促性腺激素释放激素拮抗剂(GnRH-ant)方案中促性腺激素释放激素激动剂(GnRH-a)联合低剂量绒促性素(HCG)扳机对行胚胎植入前遗传学诊断/筛查(PGD/PGS)助孕患者促排卵的效果。方法:回顾性分析2015年1月至2016年3月在我院因女方染色体异常行GnRH-ant方案中GnRH-a联合低剂量HCG双扳机诱导卵泡成熟的PGD/PGS助孕患者79例(A组),根据年龄、抗苗勒管激素(AMH)、基础卵泡刺激素(FSH)匹配选取行拮抗剂方案促排卵并单纯使用HCG扳机诱导卵泡成熟患者79例(B组)作对照,比较两组促排卵特点及促排卵结局。结果:两组促性腺激素总量、促排天数、HCG日雌二醇(E2)、HCG日孕酮(P)、HCG日黄体生成素(LH)、回收卵数、2个原核(2PN)数、第3天(D3)胚胎数、活检正常胚胎数、新发异常率差异均无统计学意义(P0.05)。与B组相比,A组获成熟卵数、D3优质胚胎数、形成囊胚数、优质囊胚数及优质囊胚率明显升高(P0.05),检测后正常的胚胎数虽然两组差异无统计学意义,但A组有升高趋势,两组OHSS发生率无明显差异(P0.05)。结论:GnRH-ant方案中GnRH-a联合HCG诱发卵母细胞成熟改善了行PGD/PGS助孕患者促排结局。     

来曲唑用于有排卵不孕症妇女的促排卵效果观察——与氯米芬的对照研究

目的 探讨来曲唑用于有排卵不孕症妇女的促排卵效果及其对生殖激素的影响。方法 选择2005-06-01—2005-10-31北京大学第三医院拟行宫腔内人工授精（IUI），或指导同房，或供精人工授精（AID）的111例有排卵的不孕症妇女，于月经周期第3～7天，每日口服来曲唑2．5mg（68例），或于月经周期第5～9天每日口服氯米芬（clomifene）50mg（43例）。超声监测卵泡发育，并于月经周期第8天和HCG日取静脉血测定黄体生成素（LH）、雌二醇（E2）、睾酮（T）和雄烯二酮（A）。当最大卵泡的平均直径／〉20mm时，肌注HCG 10000IU诱发排卵。观察排卵率、妊娠率、子宫内膜厚度及生殖激素的变化。结果 来曲唑组的排卵率和周期妊娠率与氯米芬组相似（P〉0．05），其优势卵泡数以及成熟卵泡数均显著低于氯米芬组（P〈0．01）。来曲唑组在HCG日子宫内膜的厚度显著厚于氯米芬组（P〈0、01）。其在月经周期第8天和HCG日血清E2水平均显著低于氯米芬组（P〈0、01），月经周期第8天血清A显著高于氯米芬组（P〈0．05），这种差异在HCG日消失，但血清T水平在两组之间没有差异来曲唑组在HCG日血清LH水平明显高于氯米芬组。结论 来曲唑用于有排卵的不孕症妇女，具有良好的排卵率，但其排卵率和妊娠率并未优于氯米芬，其能否作为一线的促排卵药物还需要进一步的研究结果来支持。     

不同时间使用来曲唑对Ⅱ型排卵障碍患者促排卵效果的研究

目的 探讨Ⅱ型排卵障碍患者不同时间开始服用来曲唑的促排卵治疗效果。方法 选择60例Ⅱ型排卵障碍患者,根据随机数字表法分为对照组与研究组,每组30例。研究组和对照组患者分别于月经第3天和第5天给予来曲唑。统计分析两组患者人绒毛膜促性腺激素（HCG）注射日激素水平变化及内膜厚度、促排卵效果、妊娠情况、排卵时间。结果 治疗后,两组HCG注射日促黄体生成素（LH）、雌二醇（E2）、孕酮（P）水平比较,差异均无统计学意义（P>0.05）;HCG注射日及排卵日内膜厚度比较,差异均无统计学意义（P>0.05）。虽然研究组排卵率低于对照组,但两组比较差异无统计学意义（P>0.05）。研究组排卵时间早于对照组,两组比较差异有统计学意义（P<0.05）。两组妊娠成功率比较差异无统计学意义（P>0.05）。结论 Ⅱ型排卵障碍患者在月经第3天或第5天开始服用来曲唑,对体内生殖激素、内膜厚度的影响相似,其排卵率和妊娠率均无明显差别;但月经第3天开始服用来曲唑,其排卵时间早于月经第5天开始,值得临床推广与应用。     

早孕期血绒毛膜促性腺激素值对辅助生殖治疗妊娠结局的预测价值

目的：探讨辅助生殖技术治疗后早孕期血β绒毛膜促性腺激素（β－HCG）值的单次及动态测定对预测妊娠结局的临床意义。方法：对在本中心采用辅助生殖技术治疗受孕的不孕症患者监测排卵后16天的血β－HCG值及其上升情况，追踪妊娠结局，按妊娠是否超过孕12周分为继续妊娠组及不良妊娠组。结果：血β－HCG水平与妊娠结局明显相关，排卵后16天首次血β－HCG值在继续妊娠组显著高于不良妊娠组（P＜0．01），血β－HCG＜100IU／L者87．5％有不良妊娠结局，而血β－HCG＞400IU／L，则97．3％的患者妊娠超过12周。首次验血后48小时血β－HCG的上升幅度在继续妊娠组和不良妊娠组间差异无显著性（P＞0．05）。结论：辅助生殖技术中排卵后16天单次血β－HCG值是一项有意义的预测妊娠结局的指标。     

GnRH拮抗剂方案中HCG扳机时机对胚胎的影响

目的:探讨促性腺激素释放激素拮抗剂(GnRH antagonist)方案超促排卵过程中推迟人绒毛膜促性腺激素(HCG)扳机时机对胚胎质量及妊娠率等的影响。方法:回顾性分析2015年1月至12月在我院接受体外受精-胚胎移植(IVF-ET)助孕的不孕症患者183例,均采用GnRH拮抗剂促排方案,于月经周期第2天启用促性腺激素(Gn),当有卵泡平均直径达到14mm,加用GnRH拮抗剂。按照传统HCG扳机时机(有3个≥17mm卵泡)与推迟1天扳机分为2组:早期HCG组(149例)和晚期HCG组(34例),比较两组数据。结果:HCG扳机日,晚期HCG组≥15mm的卵泡数明显多于早期HCG组(P=0.026)。晚期HCG组Gn使用天数及Gn使用总量均明显高于早期HCG组(P=0.000,P=0.012)。妊娠结局方面,晚期HCG组较早期HCG组具有更高的妊娠率(76.00%vs 50.45%,P=0.020)。两组受精率、继续妊娠率、流产率、异位妊娠率均无显著差异(P0.05)。结论:GnRH拮抗剂促排方案中,适当推迟HCG扳机时间不影响胚胎质量和妊娠率,可以推行。     

Prevention of OHSS: GnRH agonist versus HCG to trigger ovulation

Ovarian hyperstimulation syndrome (OHSS) remains a major complication of IVF. Triggering ovulation with human chorionic gonadotrophin (HCG) (as a surrogate to LH) is a major factor in the initiation of OHSS. The pathological process usually intensifies if pregnancy is achieved, as the rising endogenous HCG overstimulates the corpora lutea. Decreasing HCG trigger dose does not prevent OHSS. Gonadotrophin-releasing hormone agonists (GnRHa) induce endogenous LH and FSH surges that reliably trigger ovulation, even if a GnRH antagonist is used during ovarian stimulation. Moreover, such a trigger quickly and irreversibly induces luteolysis, thereby preventing OHSS. Contrasting reports regarding clinical outcome probably reflect different approaches to luteal phase support. Zygotes or embryos frozen post GnRHa trigger give excellent clinical outcome post thaw. In summary, GnRHa trigger is the key for complete OHSS prevention.     

Rescue of corpus luteum function with peri-ovulatory HCG supplementation in IVF/ICSI GnRH antagonist cycles in which ovulation was triggered with a GnRH agonist: a pilot study

Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI patients following a flexible antagonist protocol were prospectively randomized (sealed envelopes) to triggering of ovulation with a single bolus of either 10,000 IU of HCG (group 1, n = 15) or 0.5 mg buserelin s.c. In addition, the GnRHa triggered group was randomized into two groups: group 2 (n = 17) was supplemented with HCG 1500 IU, 12 h after ovulation induction and group 3 (n = 13) was supplemented with HCG 1500 IU 35 h after ovulation induction. Group 1 and group 3 had significantly higher luteal phase concentrations of progesterone (P < 0.001) as compared with group 2. Moreover, the clinical pregnancy rate of groups 1 and 3 was similar and significantly higher (P < 0.02) than that of group 2. A larger study, however, is required to substantiate these differences. No differences were seen regarding mid-luteal inhibin A concentrations between the three groups. Triggering of ovulation with GnRHa supplemented with 1500 IU HCG 35 h later (group 3) seems to secure a normal luteal phase and a normal clinical pregnancy outcome.     

Effects of ovulation induction agents on ovarian surface epithelium in rats

The aim of this study was to examine the effects of ovulation induction agents on the ovarian surface epithelium in rats. Sixty adult females were randomly divided into six groups, each containing 10 rats. In four of these groups ovulation induction was applied with six cycles of clomiphene citrate, human menopausal gonadotrophin (HMG), recombinant FSH (rFSH) or human chorionic gonadotrophin (HCG), respectively, followed by unilateral oophorectomy, and another six cycles of the same treatment. After a total of 12 cycles of ovulation induction, the remaining ovary was taken out and the alterations in ovarian surface epithelium were examined. No malignancies were observed on the ovarian surface epithelium of the rats that were given clomiphene citrate, rFSH or HMG as ovulation induction agents, while identification rates of histopathological parameters constituting epithelial dysplasia were found to be significant (P < 0.05). There was no significant dysplasia in the epithelium of the group which was given HCG only, relative to control groups. The findings suggest that the ovulation induction agents except for HCG bring about dysplasia in the ovarian surface epithelium. It is not clear whether these dysplasias are precursory lesions of ovarian malignancies.     

Retrospective comparison of GnRH agonist trigger with HCG trigger in GnRH antagonist cycles in anticipated high-responders

All IVF-ICSI cycles carried out between October 2009 and October 2012 using GnRH agonist (GnRHa) ovulation trigger (n = 62) followed by a single dose of HCG plus progesterone and oestradiol in the luteal phase because of anticipated ovarian hypertsimulation were retrospectively compared with historic control cycles using HCG trigger (n = 29) and standard luteal phase support. Women's mean age, body mass index, anti-Müllerian hormone, FSH, LH, starting and total stimulation dose, number of follicles, oocytes, embryos, fertilization, implantation, polycystic ovary syndrome, ICSI, live birth and ongoing pregnancy rates per embryo transfer were similar (GnRHa 40.7% versus HCG 35.0%). For each started cycle, GnRHa resulted in 11.4% higher (statistically non-significant) live birth and ongoing pregnancy rate (OR 1.73, CI 0.64 to 4.69), with a similar difference for double-embryo transfers (OR 1.62, CI 0.44 to 6.38) and less need for freezing all embryos (9.7% versus 27.6%; P = 0.04). Incidence of mild-to-moderate OHSS was 16.2% with GnRHa trigger and 31.0% with HCG trigger) and no severe OHSS in the former. The addition of single low-dose HCG in the luteal phase after GnRHa trigger for suspected high-responders reduced the incidence of OHSS with good clinical outcomes, compared with HCG trigger.     

The combination of urinary and recombinant HCG improves outcome in patients with decreased oocyte/follicle ratio in previous cycles

This report describes three cases in which the addition of recombinant HCG to urinary HCG to trigger ovulation in IVF improved oocyte recovery in patients with a history of scant oocyte yield in previous cycles.     

The impact of timing modified natural cycle frozen embryo transfer based on spontaneous luteinizing hormone surge

PurposeTo evaluate whether adjusting timing of modified natural cycle frozen embryo transfer (mNC-FET) 1 day earlier in the setting of a spontaneous LH surge has an impact on pregnancy outcomes.MethodsThis retrospective cohort study evaluated all mNC-FET with euploid blastocysts from May 1, 2016 to March 30, 2019, at a single academic institution. Standard protocol for mNC-FET included ultrasound monitoring and hCG trigger when the dominant follicle and endometrial lining were appropriately developed. Patients had serum LH, estradiol, and progesterone checked on day of trigger. If LH was ≥ 20 mIU/mL, trigger was given that day and FET was performed 6 days after surge (LH/HCG+6), with the intent of transferring 5 days after ovulation. If LH was < 20 mIU/mL, FET was performed 7 days after trigger (hCG+7). Primary outcomes included clinical pregnancy and live birth rates. To account for correlation between cycles, a generalized estimating equation (GEE) method for multivariable logistic regression was used.ResultsFour hundred fifty-three mNC-FET cycles met inclusion criteria, of which 205 were in the LH/HCG+6 group and 248 were in the HCG+7 group. The overall clinical pregnancy rate was 64% and clinical miscarriage rate was 4.8%, with similar rates between the two groups. The overall live birth rate was 60.9% (61.0% in LH/HCG+6 group and 60.9% in HCG+7 group). After implementing GEE, the odds of CP (aOR 0.97, 95% CI [0.65–1.45], p = 0.88) and LB (aOR 0.98, 95% CI [0.67–1.45], p = 0.93) were similar in both groups.ConclusionsIn our study cohort, mNC-FET based on LH/HCG+6 versus HCG+7 had similar pregnancy outcomes.     

Time to revolutionize the triggering of ovulation

Methods used for ovarian stimulation constantly change with advances in gonadotrophin therapy. In this Commentary, an appeal is made for more attention to the use of LH for the induction of ovulation. Its typical characteristics during the LH surge are finely balanced to induce normal ovulation and luteinization. It does not induce ovarian hyperstimulation, for example. The recent commercial availability of recombinant LH (LHr) offers a chance of escaping from the use of urinary human chorionic gonadotrophin (HCG) and its varied forms such as those with a shorter half-life. It should also avoid the weakly effective bursts of FSH and LH and weak luteal phases released associated with the use of gonadotrophin-releasing hormone agonists. Currently, large dosages of LHr are needed to match the endocrine events typical of inducing ovulation by the endogenous LH surge. In the interests of patients' safety and improved forms of luteal phase endocrinology, research should be devoted to improving the properties of rLH to make it induce surges similar to endogenous discharges. This would replace the current use of HCG to induce ovulation, with its attendant risks of ovarian hyperstimulation and luteal phase anomalies.     

Serum follicle-stimulating and luteinizing hormone and progesterone in single and multiple gestations following induction of ovulation

At the Mount Sinai School of Medicine in New York, researchers followed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone in 5 women treated with human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) for induction of ovulation. A total of 7 treatment cycles were followed. In 5 of the cycles conception occurred. Values in the 5 cycles in which conception occurred were dissimilar to values in normal menstrual cycles. Thus, efforts to mimic normal gonadotropin elaboration are probably unnecessary in the treatment of anovulatory women. Significant variation in values occurred among the patients. A midcycle FSH peak concomitant with the LH surge was clearly seen to be unnecessary for ovulation induction. Following ovulation a general decline in FSH occurred. FSH apparently was suppressed during the gestational period. In patients who had elevated pretreatment serum LH levels, LH apparently was suppressed during the first 1/2 of the HMG therapy; however, during the latter 1/2 of the HMG therapy, LH rose in these patients. Therapy-induced multiple ovulation with resultant multiple corpora lutea caused serum progesterone levels to rise to 2-3 times those of normal singleton gestations. Implantation appeared to have occurred 8-9 days after ovulation induction. The 5 pregnancies resulted in 3 term deliveries, 1 first-trimester spontaneous abortion, and a quadruplet premature delivery.     

Plasma estrogen monitoring of ovulation induction.

Eight hMG-hCG therapy cycles in 6 anovulatory infertile patients are presented. Daily plasma estrogen monitoring during the therapy contributed to success in inducing ovulation in all 6, 3 of whom established pregnancies and delivered healthy babies. The duration of hMG therapy required varies among individuals. Duration and dosage can be determined on the basis of daily plasma estrogen levels. Administration hCG is recommended to trigger ovulation when these levels reach 300 to 600 pg/ml. Although success in ovulation induction and pregnancy is achievable, multiple ovulation and multiple pregnancy cannot be predicted or prevented.