低促性腺激素性腺功能减退症的促排卵治疗——附2例临床分析

目的:探讨低促性腺激素性腺功能减退症的促排卵治疗方案。方法:使用hMG联合人绒毛膜促性腺激素(hCG)对2例低促性腺激素性腺功能减退症患者进行促排卵治疗,应用阴道超声和血清FSH、性激素测定监测卵泡发育。在卵泡发育成熟后给予hCG诱发排卵。结果:2例患者共进行4个周期的促排卵治疗,在给予hMG后卵泡发育缓慢或无卵泡发育时,添加hCG100~200 IU,均成功诱发排卵,并获得2例临床妊娠。结论:hMG和低剂量hCG联合使用能有效进行低促性腺激素性腺功能减退症患者的促排卵治疗。     

IVF-ET中促性腺激素释放激素激动剂的超促排卵应用与剂量研究

促性腺激素释放激素激动剂(GnRH-a)是体外受精-胚胎移植(IVF-ET)技术中重要用药。GnRH-a与GnRH受体结合后,早期"突发"作用可刺激垂体促性腺激素急剧释放,持续应用后使垂体受抑制,内源性促性腺激素(Gn)水平下降,即所谓的降调节作用。利用这种生物学特性,GnRH-a联合Gn超促排卵可预防早发黄体生成素(LH)峰,避免卵泡过早黄素化。另外,GnRH-a代替人绒毛膜促性腺激素诱发排卵可降低卵巢过度刺激综合征(OHSS)发生率。探索既能有效抑制LH峰,又不使垂体过度抑制的GnRH-a有效低剂量对于超促排卵有重要意义。     

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。     

LH在促卵泡生长和控制性超排卵中的作用

在辅助生殖技术(ART)中,促性腺激素广泛用于不孕症以治疗无排卵和控制性超排卵(COS)以诱导多个卵泡发育。为了解促黄体素(LH)在卵泡发育中的作用及在超排卵过程中是否应增加LH进行以下研究。选择50例不明原因或轻度男性因素不孕妇女,月经周期均正常,研究前3个月内未使用过妊娠激素,随机分为2组:A组予高纯度FSH(FSHHP,含FSH 75 IU/支),B组予人绝经期促性腺激素(hMG,     

低剂量绒促性素与控制性卵巢刺激

人绒毛膜促性腺激素与促性腺激素具有部分相同的结构,但其半衰期长,与受体亲和力强,在生殖医学领域除了代替黄体生成素诱发卵母细胞成熟,还用于控制性卵巢刺激(COS)。目前COS中添加低剂量绒促性素无统一时机和标准剂量,可应用于促性腺激素释放激素激动剂方案和拮抗剂方案,可在卵泡发育早期或中晚期添加,也可贯穿整个促排卵过程。目前有限的证据表明添加低剂量绒促性素可以降低卵巢刺激时的Gn用量和COS费用,能获得和常规COS方案相似的临床结局。一些特殊人群如高龄、卵巢反应不良、反复体外受精失败、低促性腺激素性闭经、黄体生成素水平过低等患者也许更能从小剂量绒促性素添加中获益。     

控制性卵巢刺激方案中扳机与取卵时机

<正>在控制性卵巢刺激(COS)方案中,一般使用促性腺激素释放激素激动剂(GnRH-a)进行垂体降调节或者促性腺激素释放激素拮抗剂(GnRH-ant)直接抑制LH峰,因此需要在卵泡发育成熟时使用外源性绒促性素(h CG)以模拟内源LH峰的作用(俗称扳机)[1],     

拮抗剂方案中hCG的临床应用

促性腺激素释放激素拮抗剂(GnRH-A)在控制性超促排卵(COH)中被用于防止早现的内源性促黄体激素(LH)峰,与GnRH激动剂(GnRH-a)相比较,GnRH-A具有以下优点:没有低雌激素副作用、没有点火效应、起效快且作用可逆。2011年最新的循证医学证据显示,GnRH-A方案联合GnRH-a促发卵子最终成熟在获得了与GnRH-a方案类似的临床妊娠率的同时,可以显著降低卵巢过度刺激综合征(OHSS)的发病率,该方案值得进一步推广和优化。但由于GnRH-A导致体内LH水平显著低于生理水平,可能影响部分患者的卵泡发育,以及GnRH-a应用后对LH活性的抑制可能对黄体功能产生不利影响,LH活性的补充成为近来研究的热点。hCG可以结合体内的LH受体,且半衰期更长、亲和力更高,其效能是LH的6倍左右,hCG在拮抗剂方案中的应用值得进一步研究。     

GnRH抗生育作用的研究进展

<正> 生理条件下,丘脑下部释放的促性腺激素释放激素(GnRH)可促进黄体生成素(LH)和卵泡刺激素(FSH)的合成与分泌,随之促进性腺的生长和发育、精子的生成、卵泡的发育和排卵、以及性激素的的合成和分泌。     

GnRH脉冲治疗的研究进展

<正>促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)脉冲治疗是利用一个微型输入装置模拟下丘脑分泌GnRH的生理模式,脉冲式皮下注射GnRH类似物,作用于垂体产生促性腺激素[黄体生成素(LH)及卵泡刺激素(FSH)]分泌脉冲,进而促进性腺发育、合成分泌性激素,最终促进并维持第二性征发育、满足患者生育需求的一种治疗方案,因符合下丘脑-垂体-性腺(hypothalamic-pituitary-gonad,HPG)轴生理调节机制,     

促性腺激素释放激素拮抗剂方案控制性促排卵过程中雌激素水平下降

血清雌激素(E_2)水平是评估控制性促排卵(COS)中卵泡发育及对促性腺激素(Gn)反应的重要指标。E_2水平的下降能否预测妊娠结局,目前尚无定论。本文分析了1例促性腺激素释放激素拮抗剂(GnRH-A)促排卵方案中出现E_2下降的案例,患者的获卵率明显下降,受精率和卵裂率正常,仅获得1枚优质胚胎,未成功妊娠,因此GnRH-A方案中E_2下降,可能会导致卵母细胞回收率下降。     

Follicle-stimulating hormone or human menopausal gonadotropin for ovarian stimulation in in vitro fertilization cycles: a meta-analysis

OBJECTIVE: To reanalyze the results of using FSH alone and hMG during IVF treatment, taking into account the different protocols of administration of superactive GnRH agonist analogs. DESIGN: Meta-analysis. SETTING: The London Women's Clinic. PATIENT(S): Women undergoing IVF treatment. INTERVENTION(S): A meta-analysis of published randomized controlled trials from 1985 to 1999 of the use of FSH versus hMG for ovarian stimulation during IVF treatment. The common Peto odds ratio was calculated with use of a fixed effect model. The overall log odds ratio was estimated after demonstrating the consistency or homogeneity of the study results. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle of IVF. RESULT(S): The results suggested that in the "long and short GnRH agonists protocol" of IVF, FSH, and hMG were equally effective in achieving ovarian stimulation, and there were no differences in the clinical pregnancy rates per cycle of IVF. However, in protocols where no pituitary desensitization was used, FSH alone was more efficacious. CONCLUSION(S): The optimum choice of gonadotropin preparation for ovarian stimulation during IVF treatment is influenced by the regimen of pituitary desensitization used. The optimum gonadotropin to be used when GnRH antagonists are used has yet to be determined.     

Effects of laparoscopic surgery on serum anti-müllerian hormone levels in reproductive-aged women with endometrioma

Objectives.?To examine and compare the effect of the two commercially available menotropins (highly purified-human menopausal gonadotropin (HP-hMG) and the traditional human menopausal gonadotropin (hMG)) on ovarian stimulation characteristics and in-vitro fertilisation (IVF) cycle outcome.

Study Design.?We studied 36 patients undergoing at least two controlled ovarian hyperstimulation cycles for IVF, with the same GnRH-analogue protocols, where one included HP-hMG and the other included hMG. Ovarian stimulation characteristics and outcome were compared between the two groups.

Results.?Patients in the HP-hMG group achieved significantly higher implantation (20.0% vs. 8.1%, p?<?0.03; respectively) and pregnancy rates (47.2% vs. 19.4%, p?<?0.009; respectively) compared to the hMG group. Although no in-between group difference was observed in the number of top-quality embryos per patient, the proportion of the total number of top-quality embryos per total number of generated embryos was significantly higher in the HP-hMG group (88/196 vs. 72/204, p?<?0.049; respectively) as compared to the hMG group.

Conclusions.?Patients undergoing controlled ovarian hyperstimulation for IVF that includes HP-hMG preparations produce significantly higher implantation and pregnancy rates, as compared to the traditional hMG.     

改良超长方案中促排卵时不同时期添加高纯度尿促性素对助孕结局的影响

目的 探讨促性腺激素释放激素激动剂(GnRH-a)改良超长方案促排卵中高纯度尿促性素(HPhMG)不同添加时机和剂量对助孕结局的影响。方法 回顾性分析本中心首次行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)中采用改良超长方案并添加使用了HP-hMG的454例患者的临床资料,根据添加HP-hMG的时机分为全程添加组(A组)和后半期添加组(B组)。A组:Gn启动日血清黄体生成素(LH)1.2 IU/L的患者在重组卵泡刺激素(r-FSH)促排卵的第1日同时添加HP-hMG至hCG注射日;B组:Gn启动日血清LH≥1.2 IU/L的患者r-FSH促排卵的第6日开始添加HP-hMG至hCG注射日。对不同年龄阶段患者(≤35岁和36~40岁)进行分析,观察Gn使用总量和使用时间、hCG注射日激素水平、获卵情况、胚胎质量、着床率、临床妊娠率、活产率、流产率和中重度卵巢过度刺激综合征(OHSS)风险等临床结果。结果 ≤35岁的患者中A组相比B组,虽然Gn使用总量有所增加,但hCG注射日孕酮(P)水平降低,IVF受精率明显增高,差异均有统计学意义(P0.05);着床率分别为58.2%和42.4%,临床妊娠率分别为80.1%和61.7%,活产率分别为68.9%和49.5%,差异均有统计学意义(P0.05)。36~40岁的患者中,A组与B组的临床妊娠率分别为61.9%和26.3%,活产率分别为47.6%和15.8%,差异均有统计学意义(P0.05)。A、B两组在不同年龄段的流产率和中重度OHSS发生率相似。结论 改良超长方案中患者全程添加HP-hMG较后半期添加能降低hCG注射日P水平,显著提高着床率、临床妊娠率和活产率。     

Medical hypophysectomy: II. Variability of ovarian response to gonadotropin therapy

In an attempt to control individual variability of ovarian response to gonadotropin therapy, ovulatory monkeys received either "pure" follicle-stimulating hormone (FSH) or human menopausal gonadotropin (hMG), with or without gonadotropin-releasing hormone (GnRH) antagonist administration. Among females that responded to gonadotropin therapy, the GnRH antagonist reduced (P less than 0.05) the variability of serum estradiol patterns. Surprisingly, after pretreatment and concurrent administration of the GnRH antagonist, FSH alone was as effective as the FSH/luteinizing hormone (LH) mixture (hMG) in stimulating follicular maturation, even when serum LH levels were at or below the limits of detection. The results indicate that in a rapidly reversible hypogonadotropic state approaching a "medical hypophysectomy," concurrent gonadotropin therapy produces a less varied ovarian response. The relative (un)importance of LH in the primate ovarian cycle seems diminished in the face of evidence that FSH alone, or in the presence of vanishingly small amounts of LH, supports follicular maturation and dynamic estrogen biosynthesis.     

IVF-ET周期中GnRH-a、FSH、hMG配伍方案的比较研究

目的:探讨IVF周期中采用不同促排卵方案时,卵泡液及血清中FSH、LH、E2水平的变化及对胚胎发育、受精、妊娠的影响;单用国产hMG促排卵的效果。方法:120例分成4组。测定卵泡液及取卵日血清中FSH、LH、E2水平,比较四种方案的取卵数、受精率、Ⅰ级、Ⅱ级胚胎形成率和每移植周期妊娠率。结果:四种促排卵方案的卵泡液和血清FSH、E2水平没有差别（P>0.05）,不同垂体降调节者,卵泡液和血清LH水平明显升高（P<0.0001）,四种促排卵方案的取卵数、受精率、优质胚胎形成率、移植周期妊娠率经统计学处理均无显著性差异。结论:卵泡液和血清中LH水平升高可能与应用垂体降调节有关,而与选择纯FSH还是hMG促排卵无关。轻度LH升高并不影响卵泡发育、卵子质量和以后的胚胎发育。IVF周期首选垂体降调节加FSH或FSH/hMG促排卵方案,单用hMG促排卵也可以作为选择。     

The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome

The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.     

The role of gonadotropins in follicular development and their use in ovulation induction protocols for assisted reproduction.

During the 1960s, hypogonadotropic patients with polycystic ovary syndrome and those with clomiphene citrate resistance were the first to achieve pregnancy after urinary human menopausal gonadotropin (hMG) administration plus preovulatory human chorionic gonadotropin injection, with cumulative pregnancy rates ranging from 40% to 80% after six to 12 treatment cycles. Ever since, dramatically more progress has been achieved regarding methods and medication in assisted conception techniques, involving both a rapidly increased number of subfertile couples, as well as many practitioners in obstetrics and gynecology. The purpose of this review was to highlight the most crucial historical steps of this remarkable process, by emphasizing the role of gonadotropins in ovulation induction protocols according to the various clinical categories of subfertile patients. In the late 1970s, urinary hMG was the most widely used gonadotropin for ovarian stimulation during in vitro fertilization-embryo transfer for assisted reproduction. The often concurrent problems of premature luteinizing hormone (LH) surges and premature luteinizations, and thus cancellations of the cycles, were efficiently overcome by 'reversible medical hypophysectomy', performed by gonadotropin releasing hormone (GnRH) analogs, introduced in 1982. According to its initiation and duration, GnRH analog use was divided into three protocols: the long, most widely used, protocol, which was the best for suppression of endogenous, high tonic LH levels, especially in polycystic ovary syndrome and normogonadotropic patients; and the short and ultra-short protocols, which were mainly used in poor responders to ovarian stimulation treatment, older or hypergonadotropic patients with ovarian failure, because of the well-known 'flare-up phenomenon'. Recently, GnRH antagonists, which directly do not permit GnRH action by binding to the GnRH gonadotropic cell receptors, have been used, but no final results from large, multicenter clinical trials that are still being undertaken have yet been achieved. Various sub-products of urinary hMG have been produced since the 1980s, with the intention of eliminating most or all of the LH, such as a form with a 3:1 proportion ratio between follicle stimulating hormone (FSH) and LH, as well as a form resulting in the removal of almost all of the LH, the 'pure' urinary FSH. Finally, in the mid-1990s, recombinant pure FSH was produced in vitro from hamster ovarian cell cultures. The theoretical basis for the broad use of pure urinary FSH and recombinant FSH is that the very low endogenous LH levels after pituitary desensitization are sufficient for proper theca steroidogenesis; still, data in the literature and clinical experience may be controversial upon that issue. From the clinical point of view, clinicians nowadays tend to stimulate polycystic ovary syndrome patients with recombinant FSH plus the application of GnRH analogs in a long protocol. However, in poor responders, patients in whom ovulation is resistant to clomiphene citrate, those older than 40 years or hypergonadotropic patients with ovarian failure, urinary hMG, because endogenous LH levels are obviously not sufficient for proper steroidogenesis in the theca cells of the follicles of these patients, is necessary in add to the administration of GnRH analogs in a short or ultra-short protocol. Regarding normogonadotropic women (the majority of patients), most authors agree with the long-protocol application of GnRH analogs. In these patients, it is not certain whether recombinant FSH alone is sufficient for the best possible induction or whether exogenous LH administration in the form of urinary hMG still remains necessary.     

The human menopausal gonadotropin (hMG) dose in in vitro fertilization (IVF): What is the optimal dose?

Conclusion Evaluating clinical studies on ovarian response, the initial hMG dose should be 150 IU hMG/day in IVF programs without GnRH cotreatment and 225 IU hMG/day in IVF programs with cotreatment with GnRH-a. Age (>35 years), basal FSH level, and body weight are variables known to affect ovarian response and, therefore, reasons to consider an increase in the initial hMG dose. In addition to a good ovarian response, ovarian stimulation with 150 IU/hMG may restrict possible adverse effects of high-dose hMG treatment on the endometrium and on the oocyte (1,12,13). Let us hope that in the future prospective randomized studies will be available to answer questions on the optimal hMG dose in different stimulation protocols.     

GnRH antagonists in normal- responder patients

To review the use of GnRH antagonists in normal-responding patients who are undergoing infertility treatment. Review article and case studies.For the normal-responding patient, GnRH antagonist protocols provide equivalent outcomes as GnRH agonist protocols, with the added patient benefit of significantly fewer treatment/injection days. In addition, a decrease or plateau in E(2) on the day after initiation of the GnRH antagonist has no prognostic significance in IVF outcome.For normal-responding patients, a GnRH antagonist can be used in a flexible fashion to achieve high success rates. The lack of correlation between E(2) patterns on the day after initiation of a GnRH antagonist and IVF outcomes supports the concept that no intervention (such as LH add-back) is necessary to guard against an early decrease or plateau during stimulation with recombinant FSH and a GnRH antagonist. Clinicians must consider ovarian physiology and the mechanism of GnRH antagonist action in patient management.     

Use of third generation gonadotropin-releasing hormone antagonists in in vitro fertilization-embryo transfer: a review

Before gonadotropin-releasing hormone agonists (GnRHa) became available, approximately 20% of stimulated cycles within an in vitro fertilization (IVF) program were cancelled due to premature LH surges. By using the GnRHa to prevent LH surges via gonadotrope GnRH receptor down-regulation and desensitization, this percentage decreased to about 2%, and concomitantly, the IVF and pregnancy rates per cycle initiated were increased. Several treatment schedules currently are in use, including the so-called "long protocol," in which the GnRHa is begun in the luteal phase and down-regulation occurs before the start of the gonadotropin-stimulation treatment phase. This is generally the most effective regimen and is presently the most frequently used protocol. However, it has some disadvantages, such as hypoestrogenic side effects and an increase in the number of ampules of FSH or hMG required for adequate stimulation. There is a new generation of GnRH antagonists now clinically available, that has been able to minimize the potential side effects and provide reliable antagonism at the GnRH receptor. These agents seem better suited than GnRHa for assisted reproductive technology (ART) cycles inasmuch as they can prevent LH surges without requiring complete gonadotropin suppression. We have reviewed the current literature concerning their use in IVF cycles.