Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective,randomized study

OBJECTIVE: To compare the use of two depot GnRH-a, leuprolide and triptorelin, in long-suppression GnRH-a protocols. DESIGN: Prospective, randomized study. SETTING: An IVF unit of an academic medical center.Fifty-two women who underwent controlled ovarian hyperstimulation and IVF. INTERVENTION(S): Patients were prospectively randomized to receive 3.75 mg depot formulations of either leuprolide or triptorelin on days 21-23 of the menstrual cycle. Stimulation with gonadotropins was initiated after pituitary desensitization was achieved. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcomes were compared between the two groups. RESULT(S): Twenty-six patients were included in each group. No significant differences were observed in the patient age, estrogen, and P levels on day of hCG administration, gonadotropin dosage, number of oocytes retrieved, fertilization rate, percentage of high-quality embryos, and number of embryos transferred. However, significantly higher clinical implantation and pregnancy rates were found in the leuprolide group compared with the triptorelin group. CONCLUSION(S): A depot preparation of leuprolide is associated with higher implantation and pregnancy rates than a depot preparation of triptorelin when it is used in the midluteal phase as part of the long-suppression GnRH-a protocol in IVF.     

Relationship between gonadotropin releasing hormone agonist dosage and in vitro fertilization outcome.

A prospective study in 132 women undergoing in vitro fertilization was performed in order to assess whether lower doses of gonadotropin releasing hormone agonists (GnRH-a) may ensure adequate oocyte retrieval and pregnancy rate, without pituitary oversuppression. Forty-five patients received subcutaneous tryptorelin depot (Decapeptyl 3.75, IPSEN SpA), 41 received subcutaneous tryptorelin acetate daily (Decapeptyl 0.1 mg, IPSEN SpA) and 46 received 0.05 mg tryptorelin acetate daily from day 21 of the cycle. From day 3 of the new cycle, if the estradiol levels were < 30 pg/ml, patients received two or three ampules of gonadotropin daily. In the group receiving subcutaneous tryptorelin acetate depot, the mean number of total gonadotropin ampules was significantly higher (p < 0.05), otherwise estradiol levels and the number of oocytes retrieved, fertilized and cleaved were significantly lower (p < 0.05). Pituitary oversuppression induced by GnRH-a causes an increase in the gonadotropin requirement for assisted reproductive techniques (ART) and a reduction in the number of oocytes retrieved and fertilized. There is a high risk of oversuppression in normal-weight or underweight women, because there is greater bioavailability of the peptide, hence elevated circulating levels of GnRH-a. Thus, ovarian stimulation in ART cycles depends on many factors, not least the identification of the best GnRH-a dose.     

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization.

OBJECTIVE: To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. RESULTS: The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. CONCLUSIONS: The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.     

GnRH analogs: depot versus short formulations

Gonadotropin releasing hormone agonists (GnRH-a) are widely used in controlled ovarian hyperstimulation (COH) for assisted reproduction (ART). Two different formulations are now available: short formulations and depot formulation. Some authors have suggested that depot GnRH-a induce a too high pituitary suppression and have put forward protocols using reduced GnRH-a doses. A reduced dose of daily triptorelin is enough for pituitary suppression during ovarian stimulation but provides no significant improvement in IVF cycle outcome when compared with depot formulation in normally responding women. However, it seems to improve ovarian response and overall results in poor responding patients. Low doses of short GnRH-a allow shorter treatment, requiring lower amounts of gonadotropins. This possibility should be considered in view of its economic advantage.     

Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization

Objective: To compare an ovarian stimulation protocol using microdose follicular phase GnRH agonist (GnRH-a) and oral contraceptive (OC) pills to a luteal phase GnRH-a protocol.

Design: Retrospective analysis.

Setting: University affiliated IVF program.

Patient(s): One hundred seventy patients who underwent IVF and ET in 1996.

Intervention(s): Patients were assigned to either a midluteal start of leuprolide acetate (LA) 1 mg/d, reduced to 0.5 mg/d after addition of gonadotropins (LUT), or OC pills until cycle day 0 followed by 20 μg of LA every 12 hours on cycle day 3 with addition of gonadotropins on cycle day 5 (MICRO).

Main Outcome Measure(s): Number of FSH ampules, days of stimulation, peak E₂, and number of oocytes retrieved.

Result(s): There were no statistically significant differences in the main outcome measures between the two groups using an age-matched ANOVA. Clinical pregnancy rate per cycle start was not statistically different (LUT = 54%, and MICRO = 37%). The cancellation rate was significantly higher in the MICRO group (22.5% vs. 8.2%).

Conclusion(s): Given the higher cancellation rate in the microdose group, a randomized clinical trial is required to determine the possible benefit of a lower dose of GnRH-a in patients with normal ovarian function.     

Performance of cryopreserved pre-embryos obtained in in vitro fertilization cycles with or without a gonadotropin-releasing hormone agonist.

OBJECTIVE: To evaluate the viability and potential for pregnancy of cryopreserved/thawed pre-embryos obtained after ovarian stimulation using gonadotropin-releasing hormone agonist (GnRH-a) adjunct therapy. DESIGN: Retrospective clinical evaluation of all patients receiving a gonadotropin ovarian stimulation protocol (follicle-stimulating hormone/human menopausal gonadotropin [FSH/hMG]) with/without GnRH-a. SETTING: Academic tertiary clinical care unit. PATIENTS: Patients receiving leuprolide acetate (LA)/FSH/hMG (n = 136: LA in the luteal phase; long protocol) were compared with patients receiving FSH/hMG alone (n = 130) within the same time-frame in our program (April 1987 through October 1989). INTERVENTIONS: All patients had both a cycle in which pre-embryos were transferred fresh and a cycle of thaw of cryopreserved pre-embryos (frozen at the pronuclear stage in a slow freeze-thaw protocol using 1,2 propanediol) transferred in monitored natural cycles. MAIN OUTCOME MEASURES: Groups were similar in age, etiology of infertility, and cycle day 3 serum FSH levels; a significantly higher (P less than 0.001) number of preovulatory oocytes was recovered in the GnRH-a group. Both groups of patients were transferred an equal number of pre-embryos at the time of IVF. Cycles with frozen/thawed pre-embryos were evaluated based on the analysis of the three main variables that demonstrate cryopreservation efficiency: survival rate, implantation rate, and term pregnancy rate (PR). RESULTS: Non-GnRH-a group (113 transfers): pre-embryo survival, 71.5%; PR/transfer, 24.7%; implantation rate, 16.0%; GnRH-a group (125 transfers): pre-embryo survival 71.6%; PR/transfer, 32.8%; implantation rate, 12.0% (no significant differences). CONCLUSIONS: The use of GnRH-a produced pre-embryos of equal aptitude for development after cryopreservation at the pronuclear stage when compared with a similar gonadotropin stimulation treatment without GnRH-a.     

高剂量来曲唑在卵巢低反应患者微刺激方案中的临床观察#br#

Objective?To explore the clinical application value of high-dose letrozole in poor ovarian response(POR) patients during mild ovarian stimulation protocols receiving IVF/ICSI. Methods?A retrospective analysis was performed on 102 patients with POR treated with letrozole mild ovarian stimulation in IVF/ICSI at our reproductive Center from January 2016 to December 2018. The high-dose letrozole group (7.5 mg/d×5 d) was the high-dose group (n=50), and the conventional letrozole group (5 mg/d×5 d) was the conventional dose group (n=52). Results?The age and basal FSH of the high-dose group were higher than those of the conventional dose group (P<0.05), and the number of sinus follicles (AFC) in the high-dose group was significantly lower than that in the conventional dose group (P<0.05). The time of use of gonadotropin (Gn) in high dose group was shorter than that in conventional dose group (P<0.05), the daily serum E2 level of human chorionic gonadotropin (hCG) was significantly decreased (P<0.05), the egg number was lower than that in conventional dose group, but the egg MⅡrate was significantly higher than that in conventional dose group (P<0.05). The clinical pregnancy rate and live birth rate per fresh transplant cycle increased in the high-dose group [55.56% vs 50%; 55.56% vs 37.5%], but the difference was not statistically significant compared with the conventional dose group (P>0.05). Conclusion?For POR patients receiving ART, high-dose letrozole with mild ovarian stimulation protocol can improve the clinical pregnancy outcome of POR patients to some extent without obvious adverse reactions, especially for POR patients with poor ovarian reserve, which may benefit from improving oocyte quality and high MII rate suggesting improved follicle quality.     

超短方案在卵巢低反应患者中的应用

目的:探讨体外受精-胚胎移植(in vitro fertilization-embryo transfer,IVF-ET)周期中,超短方案在卵巢低反应患者(poor ovarian responders,PORs)中的应用。方法:回顾性分析342例PORs的401个IVF周期,根据促排卵方案不同分为超短方案组(A组,254例,291个周期)和微刺激方案组(B组,88例,110个周期)。比较A、B组的一般资料、妊娠结局以及周期取消率等指标,分析A、B组周期取消原因。结果:临床妊娠率/移植周期、种植率和流产率组间均无统计学差异(P>0.05),但A组累积妊娠率显著高于B组(25.1%vs 14.5%,P<0.05),周期取消率显著低于B组(17.5%vs 44.5%,P<0.05)。周期取消原因分析表明,微刺激组因内膜因素取消移植的比例显著高于超短方案组(22.4%vs 7.8%,P<0.05)。结论:在PORs中,超短方案周期取消率低,患者心理压力小,整个疗程耗时短。因此超短方案也是PORs可以选择的、较理想的促排卵方案。     

Ovarian stimulation in in vitro fertilization with or without the "long" gonadotropin-releasing hormone agonist protocol: effect on cycle duration and outcome

OBJECTIVE: To study the correlation between stimulation duration of IVF cycles, with and without GnRH agonist (GnRH-a), and cycle outcome. DESIGN: Retrospective analysis of data. SETTING: University-affiliated IVF clinic. PATIENT(S): 998 IVF cycles in which long GnRH-a protocol was used, and 155 cycles with hMG only. INTERVENTION(S): IVF cycles. MAIN OUTCOME MEASURE(S): Cycle outcome in number of oocytes and embryos, and pregnancy rate. RESULT(S): The mean stimulation duration (+/-SD) was 9.6+/-1.7 and 6.7+/-1.0 for the GnRH-a and the hMG-only cycles, respectively (P<0.01). In the GnRH-a group, no statistically significant correlation between cycle duration and pregnancy rate was found. Interestingly, the patients treated for 9 days had the highest number of oocytes retrieved and the highest pregnancy rate. Stimulation duration was not affected by age in either protocol. GnRH-a cycles yielded a significantly higher number of oocytes and embryos compared to cycles without GnRH-a. The pregnancy rate was similar in both groups. CONCLUSION(S): Stimulation duration in the long GnRH-a protocol group was significantly longer than in the hMG-only group. Stimulation duration was not affected by age. No statistically significant correlation was found between stimulation duration and cycle outcome in the long protocol group.     

The gonadotropin-releasing hormone agonist stimulation test--a sensitive predictor of performance in the flare-up in vitro fertilization cycle

OBJECTIVE: To evaluate the initial versus early pattern of estradiol (E2) change after administration of a gonadotropin-releasing hormone agonist (GnRH-a), i.e., the GnRH-a stimulation test versus E2 pattern, respectively, as predictors of ovarian response and pregnancy in in vitro fertilization (IVF) patients stimulated with a flare-up protocol. DESIGN: Prospective study in a consecutive group of patients. SETTING: Tertiary care, institutional setting. PATIENTS: Two hundred twenty-eight patients entered and completed the study. The only patients excluded from study were those anticipated to have polycystic ovarian disease, those with a single ovary, or those with an ovarian cyst(s). INTERVENTIONS: Patients were stimulated with a GnRH-a flare-up protocol beginning on menstrual day 2. MAIN OUTCOME: Evaluation of the GnRH-a stimulation test and the E2 pattern as predictors of the number of mature oocytes retrieved and pregnancy. RESULTS: The GnRH-a stimulation test but not the E2 pattern was predictive of the number of mature oocytes retrieved (r = 0.53, P less than 1 X 10(-5) and pregnancy (chi 2 = 8.5, P = 0.04). The E2 pattern was predictive of the duration and number of ampules of gonadotropin required for stimulation. CONCLUSION: The GnRH-a stimulation test is a sensitive predictor of performance in the flare-up IVF cycle.     

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization-embryo transfer programs.

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin superovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program. Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7-10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39). A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively. GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.     

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。     

The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (Buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF)

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp⁶ (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women, who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P<0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%;P<0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.     

Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase--a function of improved embryo quality.

PURPOSE: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response. METHODS: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing midluteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control. RESULTS: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies. CONCLUSION: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.     

Gonadotropin stimulation following GnRH-a priming for poor responders in in vitro fertilization–embryo transfer programs

The effect of gonadotropin-releasing hormone agonist (GnRH-a) administration before gonadotropin super-ovulation on the stimulation characteristics of poor responder patients was assessed in an in vitro fertilization (IVF) program.

Thirty consecutive patients who had exhibited low ovarian response (fewer than four retrieved oocytes) in at least two previous IVF cycles (control cycles, n = 60), were eligible for the study. GnRH-a (nafarelin) was administered daily for 7–10 days from the mid-luteal phase of the previous cycle until the first day of menstruation. Menotropin treatment was commenced on cycle day 3 (with no additional GnRH-a) (study cycles, n = 39).

A significantly higher number of oocytes was retrieved (p < 0.0002) and a higher number of embryos transferred (p < 0.003) in the study cycles than in the control cycles. No cases of premature luteinizing hormone surge were recorded. Pregnancy rates per embryo transfer and per cycle were 10.4% and 7.7% for the study cycles and 2.8% and 1.6% for the control cycles, respectively.

GnRH-a, administered prior to gonadotropin treatment, should be an additional option of ovulation induction protocol for poor responders in IVF programs.     

Minimal ovarian hyperstimulation for in vitro fertilization using sequential clomiphene citrate and gonadotropin with or without the addition of a gonadotropin-releasing hormone antagonist

OBJECTIVE: To compare the results of a minimal-stimulation protocol with those of a standard protocol used for IVF. DESIGN: Retrospective, controlled study. SETTING: University center. PATIENT(S): Fifty-five patients undergoing IVF using a minimal-stimulation protocol with or without adjuvant therapy with a GnRH antagonist. A control group consisted of age- and diagnosis-matched patients undergoing a standard long GnRH agonist (GnRH-a)-gonadotropin stimulation during the same time period. INTERVENTION(S): Clomiphene citrate and gonadotropins, with or without the GnRH antagonist ganirelix. MAIN OUTCOME MEASURE(S): Oocytes recovered and pregnancy rates. RESULT(S): The number of oocytes retrieved was significantly lower for the minimal-stimulation regimen compared with the case of the long GnRH-a protocol (4.8 +/- 2.6 vs. 16.2 +/- 7.5, respectively). The clinical pregnancy rate per transfer, however, was not significantly different between the two regimens (37% vs. 41%, minimal stimulation vs. long GnRH-a protocol, respectively). The addition of ganirelix resulted in at least the same pregnancy outcome as compared with the case of cycles without the antagonist. CONCLUSION(S): Minimal stimulation using clomiphene citrate followed by gonadotropin for IVF results in pregnancy rates equal to the standard long GnRH-a-gonadotropin protocol. The addition of ganirelix resulted in at least similar results with the advantage of eliminating the occurrence of a premature endogenous LH surge.     

治疗GnRH-a引发的卵巢囊肿对体外受精结局的影响

目的:了解体外受精-胚胎移植过程中,促性腺激素释放激素激动剂(GnRH-a)引发的卵巢囊肿黄体晚期穿刺治疗对体外受精结局的影响。方法:选择2002年2月至2004年7月在我院行体外受精,黄体中期应用GnRH-a长方案的患者,其中35周期应用GnRH-a后引发卵巢囊肿,全部行囊肿穿刺治疗,设为研究组(A);对照组设为B、C两组,B组(46周期):选择与A组同期应用GnRH-a,未发现卵巢囊肿者;C组(35周期)选择与A组同期取卵进行体外受精-胚胎移植(IVF)或卵细胞浆单精子注射(ICSI)者。3组分别比较临床过程(降调满意时间、Gn的用量、获卵数)、实验室结果(受精率、卵裂率、可移植胚胎率、种植率)及结局(妊娠率、流产率)。结果:3组间临床、实验室结果及妊娠结局,统计学均无显著差异(P>0.05)。结论:黄体晚期穿刺治疗GnRH-a引发的卵巢囊肿,不影响体外受精的结局。     

CLINICAL ASSISTED REPRODUCTION: Improvement of IVF Outcome in Poor Responders by Discontinuation of GnRH Analogue During the Gonadotropin Stimulation Phase—A Function of Improved Embryo Quality

Purpose: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response.Methods: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing mid-luteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control.Results: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies.Conclusion: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.     

促性腺激素释放激素激动剂长、短方案在体外受精-胚胎移植中的比较性研究

目的　探讨促性腺激素释放激素激动剂（GnRH-a）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2000年1～5月进行IVF和单精子卵胞浆注射（ICSI）助孕的不孕患者，按病历奇、偶数编号分为GnRH-a长方案组（55例）和短方案组（54例）。长方案组从使用促性腺激素（Gn）治疗周期前的黄体中期开始使用GnRH-a0.9mg/d，至垂体完全降调节后，加用Gn；短方案组从月经第2天开始使用GnRH-a0.45mg/d，同时加用Gn。两组均在优势卵泡达18mm时，肌内注射人绒毛膜促性腺激素（hCG），36h后取卵行IVF及ICSI。结果　长方案组较短方案组，使用Gn前血清促卵泡激素（FSH）和黄体生成素（LH）水平降低［（4.4±1.2）IU/L比（6.3±1.7）IU/L,（2.7±1.5）IU/L比（4.4±2.8）IU/L,P<0.01］；注射hCG前血清雌二醇（E2）和LH水平降低［（7119±3584）pmol/L比（9523±3587）pmol/L，（1.0±1.0）IU/L比（4.0±3.4）IU/L,P<0.01］；每个卵子E2水平降低［（610±315）pmol/L比（935±450）pmol/L,P<0.01］；Gn用量增多［（28.0±8.6）支比（23.4±8.7）支,P<0.01］，用药时间增长［（11.1±1.2）d比（10.1±1.5）d,P<0.01］；两组平均获卵数、第2次成熟分裂中期卵子数、受精卵数、卵裂数、优质胚胎数及妊娠率无显著差异。结论　在IVF-ET，GnRH-a长、短方案能获得相同的控制性超排卵效果，且GnRH-a短方案能减少Gn用量和缩短治疗时间。     

基础FSH/LH比值及晚卵泡期LH水平对体外受精-胚胎移植结局的影响

目的:探讨患者基础FSH/LH比值及控制性超促排卵(COH)时降调后hCG注射日血清LH水平对IVF-ET结局的影响及与COH各参数的关系。方法:回顾性分析首次进行IVF/ICSI-ET助孕、应用GnRH-a长方案降调节的不孕妇女,共427个周期。结果:ROC曲线显示FSH/LH比值与IVF-ET临床妊娠率无明显相关性;FSH/LH≥2与FSH/LH<2组间虽然临床妊娠率无差异,但FSH/LH≥2组Gn用量增加,获卵数少,优质胚胎数少,存在统计学差异(P<0.05)。hCG注射日血清LH≥0.65IU/L者妊娠率(55.8%)明显高于LH<0.65IU/L者(24.6%)。结论:基础FSH/LH比值增高能较早反映卵巢储备功能并指导超排方案及Gn用量;降调节后卵泡晚期(hCG注射日)的LH水平过低(<0.65IU/L),将会导致临床妊娠率下降。