Cessation of Low-Dose Gonadotropin Releasing Hormone Agonist Therapy Followed by High-Dose Gonadotropin Stimulation Yields a Favorable Ovarian Response in Poor Responders

Purpose: This study is a prospective nonrandomized study to determine the effect of a new protocol of controlled ovarian hyperstimulation (COH) using low doses and a half-period of gonadotropin releasing hormone agonist (GnRHa) followed by high doses of gonadotropin in patients who were supposed to be poor responders to standard long protocols of GnRHa administration. Methods: From Dec 1996 to Nov 1998, 50 patients who were classified as poor responders were scheduled for 52 cycles of a modified controlled ovarian hyperstimulation protocol. They were categorized into 3 groups: a group of poor responders to COH in the previous IVF or IUI cycles, a group with elevated Day 3 FSH levels, and a group over the age of 40 years. All patients received GnRH agonist from the midluteal phase of the previous cycle to the onset of menstruation in the next cycle. Then high doses of gonadotropins (HMG/FSH) were given. The patients then had standard courses of in vitro fertilization and embryo transfer (IVF-ET) or transfallopian embryo transfer (TET). Results: Six of the 52 cycles of the modified protocols were cancelled because of poor ovarian response. One premature ovulation was noted before ovum retrieval was performed. In the other 45 cycles, an average of 6.3 mature oocytes were retrieved. The total pregnancy rate and implantation rate were 20.5 and 11.5%, respectively. Conclusions: The low dose and half duration of GnRHa therapy lessened the suppression of the response of the ovaries to COH compared with the regular long protocol of GnRHa down regulation therapy. This resulted in a low cancellation rate (11.8%), a favorable embryo implantation rate (11.5%), and an acceptable clinical pregnancy rate (20.5%).     

来曲唑联合促卵泡素在PCOS患者IVF-ET中的应用及效价分析

目的:探讨来曲唑(LE)联合FSH在多囊卵巢综合征(PCOS)患者IVF-ET或ICSI中的应用及效价分析。方法:回顾性分析接受IVF-ET/ICSI治疗的170名PCOS不孕患者,分为LE组(LE-FSH组,n=59)与对照组(GnRHa-FSH组,n=111)。比较组间促排卵、妊娠结局、每周期治疗费用及药物效价比。结果:LE组和对照组FSH用药天数分别为6.3±1.9 d vs 13.0±2.3、用药量为615.6±284.6 IU vs l 504.9±424.9 IU,组间比较有显著性差异(P<0.01);hCG注射日E2值分别为1 965.3±1119.7 pmol/L vs 12 660.2±7 254.2 pmol/L,获卵数分别为6.5±3.3 vs16.6±7.9,组间比较均有显著性差异(P<0.01);受精率、胚胎种植率分别为66.1%vs71.6%,25.58%vs 23.63%,临床妊娠率为49.12%vs 34.48%,组间比较无显著性差异(P>0.05);中-重度OHSS发生率分别为O%和6.89%,组间比较差异有显著性(P<0.01)。LE组每刺激周期药费(2 877±1 240元)及每妊娠周期药费(3 014±1581元)显著低于对照组(6 561±1 852元、8774±1970元)(P<0.01),治疗效价比分别为5 959元vs 30 067元。结论:LE联合促卵泡素可有效运用于PCOS患者的IVF-ET中,较传统的GnRHa-FSH促排卵相比,无OHSS的发生、费用低、效价比高,且不影响妊娠率和种植率。     

来曲唑/FSH促排卵中GnRHa与hCG诱发卵泡成熟效果的比较

目的:比较曲普瑞林和hCG在来曲唑(LE)/FSH促排卵行IVF-ET治疗中诱发卵泡成熟的效果。方法:391个IVF-ET治疗周期随机分成促性腺激素激动剂(GnRHa)组(n=267)和hCG组(n=124),所有患者均采用LE/FSH促排卵方案,当主导卵泡平均直径达18～20mm时,GnRHa组患者采用达菲林0.1mg诱导卵泡成熟,hCG组采用hCG10000IU诱导卵泡成熟,比较组间的获卵数、MII卵率、受精率、卵裂率、优胚率、临床妊娠率和中-重度卵巢过度刺激综合症(OHSS)发生率。同时比较两组患者诱导日(d0)、取卵日(d2)、胚胎移植前日(d4)和胚胎移植后第4日(d9)的血清E2、P、LH水平。结果:hCG组Gn使用总量、MII卵率、卵裂率、中-重度OHSS发生率显著高于GnRHa组(P<0.05)。Gn使用天数、获卵数、受精率、种植率、临床妊娠率、流产率组间无统计学差异(P>0.05)。GnRHa组d0LH、d2LH、d9LH水平显著高于hCG组(P<0.05),而d2P、d4E2、d4P、d4LH、d9E2、d9P水平显著低于hCG组(P<0.05)。结论:在LE/FSH促排卵方案中可以用GnRHa替代hCG诱导卵泡成熟,而不影响IVF结局,并显著降低OHSS发生率。GnRHa诱导卵泡成熟的IVF周期其黄体期存在黄体功能不全,需适当补充外源性hCG加强黄体支持。     

Agonist depot versus OCP programming of frozen embryo transfer: a retrospective analysis of freeze-all cycles

Purpose

In segmented ART treatment or so-called ‘freeze-all’ strategy fresh embryo transfer is deferred, embryos cryopreserved, and the embryo transferred in a subsequent frozen embryo transfer (FET) cycle. The purpose of this cohort study was to compare a GnRHa depot with an oral contraceptive pill (OCP) programming protocol for the scheduling of an artificial cycle FET (AC-FET) after oocyte pick-up (OPU).

Methods

This retrospective cohort study was conducted on prospectively performed segmented ART cycles performed between September 2014 and April 2015. The pregnancy, treatment duration, and cycle cancellation outcomes of 170 OCP programmed AC-FET cycles were compared with 241 GnRHa depot programmed AC-FET cycles.

Results

No significant difference was observed in the per transfer pregnancy and clinical pregnancy rates between the OCP and GnRHa groups, 72.0 versus 77.2 %, and 57.8 versus 64.3 %, respectively. Furthermore, the early pregnancy loss rate was non-significantly different between the OCP and GnRH protocol groups, 19.8 versus 16.7 %, respectively. However, nine (5.29 %) cycles were cancelled due to high progesterone in the OCP protocol group, while no cycles were cancelled in the GnRHa protocol group and the time taken between OPU and FET was 19 days longer (54.7 vs 35.6 days) in the OCP protocol compared to the GnRHa protocol.

Conclusions

The results of this AC-FET programming study suggests that the inclusion of GnRHa depot cycle programming into a segmented ART treatment will ensure pregnancy, while significantly reducing treatment duration and cycle cancellation.

     

长方案使用短效GnRHa未完全降调节联合应用长效GnRHa的体外受精-胚胎移植结局分析

目的:探讨长方案控制性超排卵(COH)短效醋酸曲普瑞林(Gn-RHa,0.1mg/支)未完全降调节,联合应用长效GnRHa对体外受精-胚胎移植(IVF-ET)结局影响。方法:回顾性分析本中心采用IVF-ET助孕长方案降调节治疗96个周期,根据用药后是否达到降调节标准,分为达标组(A组,n=72例)、未达标组(B组,n=24例);未达标组为避免取消周期,继续采用长效GnRHa(3.75或1.875mg)再降调节16～18天后行超促排卵治疗,分析两组超促排卵情况以及妊娠结局。结果:B组短效GnRHa降调节14天后FSH、E2、P、内膜厚度未达到降调节标准,结果均高于A组及B组补救长效GnRHa降调节后(P<0.05);B组(补救后)LH、E2低于A组,差异有显著性(P<0.05)。B组Gn天数、用量高于A组(P<0.05);B组HCG日LH、E2、≥14mm卵泡数、平均获卵数均低于A组(P<0.05);两组MⅡ率、受精率、优胚率、种植率、临床妊娠率、流产率,取消周期率,OHSS率无显著性差异(P>0.05)。结论:长方案短效GnRHa降调节未达标准者,于本周期内行长效GnRHa再次降调节,降低了周期取消率,仍可达到较高妊娠率。     

Prolonging GnRH-agonist to achieve ovarian suppression does not compromise the results of a long protocol

Objectives

In the long gonadotropin-releasing hormone agonist (GnRHa) protocols, stimulation is delayed until complete pituitary-ovarian suppression has been achieved, which usually takes a minimum of 10 days. In women who do not achieve timely suppression we set out to evaluate if prolonging GnRHa affects the results of the IVF process.

Study design

We analyzed cycle and pregnancy outcome in 506 consecutive women undergoing IVF-ET after a standardized long GnRHa protocol, according to the time required to achieve ovarian suppression (i.e. estradiol < 40 pg/mL and no follicle >6 mm at ultrasound).

Results

Suppression was obtained after 14 GnRHa days in 383 (75.70%) women (Group 1) and 123 (24.30%) women (Group 2) required a mean ± SD (range) of 10 ± 4 (7-28) additional days to achieve complete suppression. Both groups were comparable for baseline clinical and biological characteristics. The rate of cancelled cycles due to poor ovarian response, the number of the oocytes retrieved, fertilization rates, the number and quality of the embryos cultured and transferred were similar in both groups, as well as the pregnancy, implantation and live birth rates. In Group 2, receiver-operator characteristics analysis showed that the probability of pregnancy was not related to the duration of GnRHa treatment.

Conclusions

In a standardized long GnRHa protocol, prolonging desensitization to achieve complete ovarian suppression does not affect the outcome.     

胚胎移植12 491个周期的临床效果及影响因素分析

目的 探讨体外受精-胚胎移植(IVF-ET)治疗不孕的临床效果及其影响因素.方法 回顾性分析北京大学第三医院2005至2007年间,12 491个胚胎移植周期(其中6832个周期为新鲜胚胎移植周期,5659个周期为冻融胚胎移植周期)的临床资料,对影响妊娠结局的因素进行单因素和多因素分析.结果 新鲜胚胎移植周期临床妊娠率为32.99%(2254/6832),活产率为25.75%(1394/5413),早期流产率为9.36%(211/2254),围产儿出生缺陷率为1.45%(25/1722).年轻(20～24岁)患者新鲜胚胎移植周期临床妊娠率高达42.25%(60/142).单纯男方因素不孕患者的临床妊娠率(40.10%,476/1187)明显高于单纯女性因素不孕患者(31.55%,1168/3702)和双方因素不孕患者(31.39%,610/1943);首次接受IVF-ET治疗者的临床妊娠率(34.63%,1831/5287)高于多次接受IVF-ET治疗者;常用的4种IVF-ET超促排卵(COH)治疗方案中,接受促性腺激素释放激素激动剂(GnRH-a)超长方案和长方案治疗者临床妊娠率分别为51.72%(30/58)和36.88%(489/1326),明显高于GnRH-a短方案(32.05%,1703/5313)和促性腺激素释放激素拮抗剂(GnRH-ant)方案(22.12%,23/104),差异有统计学意义(P<0.05).多因素logistic分析证实,年龄、获卵数和COH治疗周期数对IVF-ET治疗后妊娠结局的影响有统计学意义,而年龄是最主要的影响因素.治疗过程中,中重度卵巢过度刺激综合征(OHSS)的发生率为3.68%(321/8720),异位妊娠率为6.12%(138/2254),早期流产率为9.36%(211/2254).冻融胚胎移植周期临床妊娠率(38.08%,2155/5659),高于新鲜胚胎移植周期(32.99%,2254/6832),两者比较,差异有统计学意义(P<0.001);多胎妊娠率为27.70%(597/2155),早期流产率为8.96%(193/2155),异位妊娠率为2.23%(48/2155).结论 IVF-ET用于不孕症治疗,临床妊娠率和活产率高,是一种安全、有效的助孕治疗方法;年龄、卵巢反应性是影响治疗结局的主要因素;冻融胚胎移植周期临床妊娠率与新鲜胚胎移植周期比较,无明显差异,并可有效提高单次促排卵周期的累计妊娠率.     

Early pituitary desensitization and ovarian suppression with leuprolide acetate is associated with in vitro fertilization-embryo transfer success

OBJECTIVE: To determine if the timing of the onset of pituitary desensitization and ovarian suppression using follicular phase leuprolide acetate (LA) is associated with in vitro fertilization-embryo transfer (IVF-ET) success for pregnancy. DESIGN: Retrospective series of IVF patients undergoing pituitary desensitization and ovarian suppression before beginning controlled ovarian hyperstimulation for IVF-ET. SETTING: Tertiary infertility practice. PATIENTS: Seventy-eight women for 80 cycles began LA on day 1 of their menstrual cycle. After 11 days of LA, 47 (59%) cycles in group I had suppressed serum estradiol (E2) levels less than 40 pg/mL, in contrast to 33 (41%) cycles in group II not adequately suppressed, thereby requiring additional days to achieve suppression. INTERVENTIONS: Controlled ovarian hyperstimulation was started when patients were satisfactorily suppressed, i.e., E2 less than 40 pg/mL. MAIN OUTCOME MEASURE(S): Mean E2 response, ampules of human menopausal gonadotropin, cancellation rates, number of oocytes retrieved, fertilization rates, and pregnancy rates (PRs) per cycle were examined between groups I and II. RESULTS: Group I demonstrated a greater mean E2 response on the day of human chorionic gonadotropin 1,735 pg/mL versus 1,470 pg/mL (P = 0.008), a greater fertilization rate 64% versus 55% (P = 0.02), and a higher PR per cycle 34% versus 12% (P = 0.036) compared with group II. CONCLUSIONS: Women who achieved desensitization-suppression within 11 days of initiating LA demonstrated a more favorable outcome for IVF-ET than those who did not.     

Does Surgical Management of Endometriosis Within 6 Months of an In Vitro Fertilization–Embryo Transfer Cycle Improve Outcome?

Purpose : To assess the effect on cycle outcome of surgery for endometriosis performed in the 6 months prior to in vitro fertilization–embryo transfer (IVF-ET). Methods : Retrospective analysis of all patients with a primary diagnosis of endometriosis undergoing IVF-ET during 12 consecutive months. The setting included tertiary care assisted reproductive technology program. Ninety-five consecutive cycles in candidates for autologous IVF-ET who had undergone surgical resection of endometriosis within 60 months of oocyte retrieval were evaluated. Five patients with persistent or recurrent endometriomas >3 cm at the time of IVF-ET were excluded. Patients were divided into two groups based on the interval between the most recent surgical intervention and oocyte aspiration—Group I: 6 months' interval (19 cycles); Group II: >6 months' interval (76 cycles). Results : Mean intervals between surgery and oocyte aspiration were significantly different between the groups (Gr I: 3.7 ± 0.3 months; Gr II: 21.8 ± 1.6 months; p < 0.001). There were no significant differences between groups with regards to age, extent of endometriosis, or results of ovarian stimulation and oocyte aspiration. Ongoing pregnancy rates (Gr I: 63.2%; Gr. II: 60.5%) were similar. Regression analyses revealed no correlation between implantation rates and either endometriosis score (r = –0.09) or surgery–oocyte aspiration interval (r = –0.13). Conclusions : The interval between surgical management of endometriosis and oocyte aspiration did not have an impact on IVF-ET cycle outcome in the absence of significant persistent or recurrent ovarian disease. Any effect of surgery on enhancing spontaneous conception may be overcome by the inherently greater impact of IVF-ET on implantation and pregnancy.     

Pregnancy outcomes after frozen-thawed single euploid blastocyst transfer following IVF cycles using GNRH agonist or HCG trigger for final oocyte maturation

To assess whether GnRH agonist trigger impacts the implantation potential of euploid embryos. Retrospective cohort study done at an academic IVF center evaluating frozen-thawed embryo transfer (FET) cycles in which single-euploid blastocysts were transferred between 2014 and 2019. All embryos were generated in an IVF cycle which used GnRHa or hCG trigger and then were transferred in a programmed or natural FET cycle. Only the first FET cycle was included for each patient. Primary outcome was ongoing pregnancy rate or live birth rate (OPR/LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), clinical loss rate (CLR), and multiple pregnancy rate (MPR). Logistic regression was performed to control for confounding variables. A p value of < 0.05 was considered statistically significant. Two hundred sixty-three FET cycles were included for analysis (GnRHa = 145; hCG = 118). The GnRHa group was significantly younger (35.2 vs. 37.5 years) and had higher AMH values (4.50 ng/ml vs. 2.03 ng/ml) than the hCG group, respectively (p < 0.05). There was no significant difference in OPR/LBR (64.1% (93/145) vs. 65.3% (77/118); p = 0.90) between the GnRHa and hCG groups, respectively. There was also no significant difference in IR, CPR, CLR, or MPR between groups. After controlling for confounding variables, the adjusted odds ratio for OPR/LBR was 0.941 (95% CI, 0.534–1.658); p = 0.83) comparing GnRHa to hCG. Pregnancy outcomes did not significantly differ when groups were stratified by age (< 35 vs. > 35 years old). Our findings confirm that euploid embryos created after hCG or GnRHa trigger have the same potential for pregnancy.     

A prospective study of prognostic factors in in vitro fertilization and embryo transfer

Multiple factors influence the outcome of in vitro fertilization and embryo transfer (IVF-ET). This prospective study was designed to assess their relative importance, in order to improve prognostic ability and treatment success. Prior to IVF-ET, couples were divided into "good" (GP) and "poor" (PP) prognosis groups according to female age, semen quality, previous response to stimulation, and embryo quality. The data obtained from 716 consecutive treatment cycles then were evaluated using univariate statistics and logistic regression, a technique designed to assess the relative contribution of significant factors. The pregnancy rate per GP cycle was 14.7%, compared with 5.4% per PP cycle (chi 1(2) = 12.7, P less than 0.001). The most important prognostic factors were female age, the pregnancy rate showing a linear decline after the age of 25, and previous failed fertilization due to abnormal sperm. The rate of pregnancy also declined after 14 or more follicles were aspirated and/or nine oocytes were retrieved. A formula for the probability of pregnancy, derived from the logistic regression, provides patients with a more accurate prognosis before treatment.     

The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET)

The use of gonadotropin releasing hormone agonists (Gn-RHa) has been shown to improve the response in patients classified as poor responders undergoing ovarian stimulation for in vitro fertilization/embryo transfer (IVF/ET). This study sought to determine whether GnRHa therapy would benefit patients undergoing IVF/ET who had been classified as good responders in prior attempts. Twenty-three patients who had completed a prior IVF/ET attempt but who failed to conceive underwent ovarian stimulation using a combination of GnRHa and human menopausal gonadotropin (hMG). Each patient's prior stimulation served as her control and consisted of clomiphene citrate (CC)/hMG in 18 patients and follicle stimulating hormone (FSH) and/or hMG in 5 patients. The numbers of oocytes retrieved, oocytes fertilized, embryos cleaved, and embryos transferred were all significantly greater in cycles treated with GnRHa/hMG compared to control cycles. The clinical pregnancy rate was 39% and the ongoing pregnancy rate was 26% during the cycle when GnRHa pretreatment was utilized. These data suggest that GnRHa therapy is of benefit even to those patients previously classified as good responders undergoing ovarian stimulation for IVF/ET.Presented at the 45th Annual Meeting of the American Fertility Society, November 1989, San Francisco, California.     

Significance of an abnormal response during pituitary desensitization in an in vitro fertilization and embryo transfer program

Purpose: Our purpose was to evaluate the IVF-ET outcome in patients who did not achieve timely pituitary-ovarian suppression following long-protocol GnRH agonist (GnRH-a) administration. Methods: A retrospective analysis was done on 96 IVF treatment cycles characterized by a delayed response (DR) to long-protocol GnRH-a treatment. The study included those patients who either achieved ovarian suppression (E₂ 110 pM) despite an elevated LH level (group DR-A) or had pituitary desensitization (LH 1.5 IU/L) without ovarian suppression (group DR-B) on day 12 of GnRH-a treatment but needed an extended course of GnRH-a treatment to achieve complete suppression. These patients had gonadotropin stimulation either from day 12, despite an elevated level of LH (subgroup DR-A1; n=13) or elevated E₂ levels (subgroup DR-B1; n=9), or after achieving a complete hypogonadotropic-hypopgonadal state following an extended course of GnRH-a treatment [subgroups DR-A2 (n=46) and DR-B2 (n=28)]. The outcome was compared with that of 88 cycles of normal responders (group NR) who had pituitary-ovarian suppression by day 12 of GnRH-a administration. Results: Ovarian response and pregnancy rates in subgroups DR-A1 and DR-A2 were statistically not different and comparable to those in the NR group. In subgroups DR-B1 and DR-B2, E₂ response and rates of oocyte retrieval and pregnancy were significantly lower than those in the other groups, but fertilization and cleavage rates were similar. The requirement of gonadotropin for ovarian stimulation was comparatively higher in subgroup DR-A2 and both DR-B subgroups. Conclusions: There was no treatment cancellation in group NR and both DR-A subgroups, but 22% of the cycles in DR-B1 and 14% of the cycles in DR-B2 were canceled due to poor ovarian response. It therefore appears that during long-protocol pituitary desensitization, the post-GnRH-a level of serum E₂, rather than LH, better predicts IVF-ET outcome.Presented in part at the XIth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.     

控制性超排卵长、短方案在IVF-ET中的疗效比较

目的:比较促性腺激素释放激素激动剂(GnRHa)长、短方案控制性超排卵在体外受精-胚胎移植(IVF-ET)中的疗效。方法:将2001年7月-2002年4月因双侧输卵管梗阻IVF-ET的患者100人随机分为长方案组(50人)和短方案组(50人)进行超排卵。长方案组从使用促性腺激素(Gn)治疗前1月经周期黄体期(月经21天)使用GnRHa 0.3mg/d,至垂体完全降调节后加用Gn;短方案组从月经周期第2天开始用GnRHa0.1mg/d,同时加用Gn。当患者有3个以上卵泡直径>18mm时肌肉注射人绒毛膜促性腺激素(HCG),36小时后取卵行IVF,取卵48小时后行ET。结果:两组患者平均获卵数、受精率、卵裂率、优质胚胎率、移植胚胎数、临床妊娠率、胚胎种植率及流产率差异无显著性。而两者的Gn使用量有差别,短方案组少于长方案组,两组差异有显著性。两组用Gn第7天雌激素水平不同,短方案组明显高于长方案组,两者差异有显著性。结论:GnRHa长、短方案在IVF-ET中控制性超排卵效果相同,但所需Gn数量不同。     

促排卵过程中子宫内膜厚度变化对IVF-ET结局的影响

目的:探讨促排卵过程中子宫内膜厚度变化趋势对IVF结局的影响,以及不同促排卵方案对子宫内膜厚度变化趋势的影响。方法:回顾性分析1 173个IVF-ET周期,控制性促排卵方案包括:长方案(568例)、口服避孕药(OC)+GnRHa方案(425例)、拮抗剂方案(107例)和超长方案(73例)。比较各种促排卵方案的妊娠组与非妊娠组的子宫内膜厚度变化情况,包括Gn启动当日、启动后第5日、hCG注射日及子宫内膜差值1(=启动后第5日内膜厚度-启动当日内膜厚度)、子宫内膜差值2(=hCG注射日内膜厚度-启动后第5日内膜厚度)、子宫内膜差值3(=hCG注射日内膜厚度-启动当日内膜厚度)。结果:hCG注射日子宫内膜厚度妊娠组均较未妊娠组显著增加(P<0.05);Gn启动当日子宫内膜厚度、促排卵第5日子宫内膜厚度、子宫内膜厚度差值1、差值2、差值3妊娠组与未妊娠组间均无统计学差异(P>0.05)。结论:促排卵过程中子宫内膜厚度的变化趋势不能预测IVF结果,不同的促排卵方案不影响子宫内膜厚度的变化趋势。     

In Vitro Fertilization with Low-Dose Clomiphene Citrate Stimulation in Women Who Respond Poorly to Superovulation

Purpose: Our experience with IVF using low-dose clomiphene citrate for stimulation in non- and poor responders was reviewed and the treatment outcomes with the previous controlled ovarian stimulation cycles in which hMG and GnRH agonist were used were compared. Methods: The treatment outcome in 11 non- and 20 poor responders having 30 and 53 clomiphene citrate IVF treatment cycles, respectively, were compared with the treatment outcome in the previous long-protocol buserelin/hMG cycles. Results: The clinical pregnancy rates per oocyte collection achieved in the first clomiphene citrate cycle in non (9.1%)- and poor (10%) responders were comparable to those achieved by poor responders (11.9%) who had buserelin/hMG using the long protocol. Although the numbers were small, a similar pregnancy rate could still be achieved in poor responders up to the third attempt using clomiphene citrate. Conclusions: IVF using long-protocol buserelin/hMG is more successful than using clomiphene citrate stimulation. However, this advantage may not be significant in those women with a previous poor response to buserelin/hMG. It is suggested that for such poor responders, three attempts of IVF in a clomiphene citrate cycle may offer a viable therapeutic alternative before reverting to more stressful, expensive, and time-consuming treatment.     

GnRH agonist versus GnRH antagonist in poor ovarian responders: a meta-analysis

The aim of this meta-analysis was to compare the efficacy of gonadotrophin antagonist (GnRH-ant) versus GnRH agonist (GnRHa) as coadjuvant therapy for ovarian stimulation in poor ovarian responders in IVF/intracytoplasmic sperm injection cycles. Search strategies included on-line surveys of databases such as MEDLINE , EMBASE and others. A fixed effects model was used for odds ratio (OR) and effect size (weighted mean difference, WMD). Six trials fulfilled the inclusion criteria (randomized controlled trials). There was no difference between GnRH-ant and GnRHa (long and flare-up protocols) with respect to cycle cancellation rate, number of mature oocytes and clinical pregnancy rate per cycle initiated, per oocyte retrieval and per embryo transfer. When the meta-analysis was applied to the two trials that had used GnRH-ant versus long protocols of GnRHa, a significantly higher number of retrieved oocytes was observed in the GnRH-ant protocols [P=0.018; WMD: 1.12 (0.18, 2.05)]. However, when the meta-analysis was applied to the four trials that had used GnRH-ant versus flare-up protocols, a significantly higher number of retrieved oocytes (P=0.032; WMD: -0.51, 95% CI -0.99, -0.04) was observed in the GnRHa protocols. Nevertheless, additional randomized controlled trials with better planning are needed to confirm these results.     

3种控制性促排卵方案治疗卵巢反应不良效果的比较

目的:探讨3种控制性促排卵方案治疗卵巢反应不良年轻患者的效果。方法:回顾分析2009年6月至2011年7月在中山大学附属第一医院生殖中心行辅助生育治疗、年龄30～40岁、出现2次及以上卵巢反应不良周期患者的所有周期共240个,选取其中标准GnRH激动剂长、短及拮抗剂方案共220个周期。在220个周期中GnRH激动剂长方案86个周期为长方案组、短方案83个周期为短方案组、拮抗剂方案51个周期为拮抗剂方案组。比较3组病例的临床资料、实验室资料和妊娠结局,评估不同促排卵方案治疗卵巢反应不良的结果。结果:短方案组基础FSH高于长方案组(P=0.039),但Gn总量少于长方案组(P=0.000),两组胚胎质量及妊娠结局的差异无统计学意义。短方案组基础FSH与拮抗剂方案组的差异无统计学意义,虽然Gn使用量高于拮抗剂方案组(P=0.000),但获卵数亦高于拮抗剂方案组(P=0.001),且周期取消率低于拮抗剂方案组(P=0.013)。3组其他临床资料(年龄、不孕年限等)、受精数、受精率、可利用胚胎率、胚胎种植率及妊娠结局等差异均无统计学意义(P>0.05)。比较添加生长激素对长、短方案获卵数的影响,差异无统计学意义(P>0.05)。结论:GnRHa短方案用于小于40岁的卵巢反应不良患者的促排卵效果较优。     

Cycle-specific and cumulative fecundity in patients with endometriosis who are undergoing controlled ovarian hyperstimulation-intrauterine insemination or in vitro fertilization-embryo transfer

OBJECTIVE: To compare controlled ovarian hyperstimulation-intrauterine insemination (COH-IUI) or IVF-ET pregnancy rates per cycle (PR) and cycle and cumulative fecundity (f and cf) with COH-IUI or IVF-ET in endometriosis. DESIGN: Retrospective analysis. SETTING: Endometriosis research institute. PATIENT(S): Women with endometriosis and infertility (n = 313) who underwent consecutive COH-IUI (202 patients, 648 cycles), IVF-ET (111 patients, 139 cycles), or IVF-ET after failed COH-IUI (56 patients, 68 cycles). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Crude PR and life table-estimated f and cf. RESULT(S): With COH-IUI, 69 patients conceived; 65 conceived with IVF-ET; and 30 conceived with IVF-ET after COH-IUI (PR 11%, 47%, and 44%). With COH-IUI, six-cycle cf was 41%, and f for cycles 1-6 was 15%, 12%, 8%, 7%, 7%, and 0. With IVF-ET, three-cycle cf was 73%, whereas f for cycles 1-3 was 47%, 27%, and 33%. First-cycle f with IVF-ET was significantly higher than cf of six COH-IUI cycles. When the data were stratified according to the stage of endometriosis and women's age, the benefit of IVF over COH was even more pronounced. Prior COH-IUI failure did not adversely affect IVF-ET outcome. CONCLUSION(S): In endometriosis, PR, f, and cf are significantly higher with IVF-ET than COH-IUI, especially in stage IV and in women >38 years of age. Considering adverse effects of prolonged ovarian stimulation on endometriosis, IVF-ET should be the first-line approach in the management of infertility in this disease. If COH-IUI is attempted, it should not exceed three to four cycles.     

The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta-analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment.