Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins

To avoid cancellation of in vitro fertilization (IVF) because of early luteinization, pituitary suppression by gonadotropin-releasing hormone (GnRH) was carried out in 111 cycles. D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules were administered intramuscularly at menstruation and menotropin (hMG) stimulation was started 19 days (mean) later. In 3 cycles (2.7%), only early luteinization occurred. The mean number of oocytes per cycle was 6.7, with a fertilization and cleavage rate of 50 and 95%, respectively. A mean of 3.4 embryos were transferred per cycle. The 111 cycles resulted in 34 clinical pregnancies, 41% per cycle with embryo transfer. The early abortion, multiple pregnancy, and ovarian hyperstimulation rates were 24, 18, and 11%, respectively. It is concluded that D-Trp-6-LH-RH/hMG cycles are associated with a very low occurrence of early luteinization, high number of oocytes and embryos, and a substantial incidence of ovarian hyperstimulation syndrome.     

Immaturity and aneuploidy in human oocytes after different stimulation protocols

OBJECTIVE: To study immaturity and aneuploidy in human oocytes after two different stimulation protocols. DESIGN: Retrospective. SETTING: Outpatient IVF clinic/laboratory. PATIENTS: One hundred forty-three patients of whom 65 were stimulated with clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 78 were stimulated with gonadotropin-releasing hormone agonist (GnRH-a)/hMG. Only patients with at least one oocyte unfertilized were included in this study. RESULTS: Stimulation with GnRH-a/hMG, as compared with CC/hMG stimulation, resulted in larger numbers of oocytes (P less than 0.00001), a higher fertilization rate (P less than 0.02), and oocyte retrieval at a later average cycle day (P less than 0.000005). Cytogenetic findings of immaturity were observed in 33.9% of unfertilized oocytes after CC/hMG stimulation, compared with only 17.8% after GnRH-a/hMG stimulation (P less than 0.0005). Aneuploidy findings were the same for both groups. CONCLUSION: In GnRH-a/hMG stimulation, oocytes approach the normal day of ovulation more closely. This may allow for better oocyte maturation and higher fertilization and pregnancy rates.     

Ovarian stimulation protocol for in vitro fertilization with gonadotropin-releasing hormone agonist widens the implantation window

Pregnancy rates vary considerably with the type of ovarian stimulation used for in vitro fertilization and embryo transfer (IVF-ET). The window of implantation may represent one of the rate-limiting steps in IVF success. We therefore investigated estimated implantation times of 10 consecutive IVF singleton pregnancies, achieved using pituitary suppression with gonadotropin-releasing hormone agonist (GnRH-a) before and during ovarian stimulation with human menopausal gonadotropins (hMG), and compared those with 9 consecutive IVF pregnancies achieved by hMG stimulation only. Estimated implantation times were calculated by regression analysis of serial human chorionic gonadotropin (hCG) measurements between days 7 and 16 after ET. The GnRH-a/hMG pregnancies implanted between days 7 and 11, whereas hMG pregnancies implanted between days 7 and 9 after ET. The hCG regression curve for the GnRH-a/hMG pregnancies revealed a delay of 1.5 days in estimated implantation time compared with the hMG only group. There were no significant differences in pretransfer in vitro embryos development between the two groups. Thus, the delay in hCG rise probably reflects a delay in embryo implantation. We therefore conclude that a GnRH-a/hMG stimulation protocol appears to widen the implantation window in comparison with a hMG only protocol. This observation may at least in part explain the improved IVF pregnancy success with GnRH-a/hMG stimulation protocols.     

The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study.

OBJECTIVE: To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage. DESIGN: Prospective randomized study. PATIENTS: Three hundred eight patients having their first ever IVF attempt. INTERVENTIONS: Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n = 81); clomiphene citrate and hMG (group B, n = 77); a 3-day ultrashort course of GnRH-a and hMG (group C, n = 74); or pituitary desensitization with GnRH-a followed by hMG (group D, n = 76). RESULTS: The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer. CONCLUSION: The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages.     

Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone.

OBJECTIVE: To compare the in vitro fertilization and embryo transfer (IVF-ET) outcome of a 3-day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. DESIGN: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. SETTING: The IVF-ET program. MAIN OUTCOME MEASURES: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. RESULTS: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. CONCLUSION: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH-a protocol, is inferior in its outcome compared with the two other protocols.     

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.     

A comparative study of three ovulation induction protocols in polycystic ovarian disease patients in an in vitro fertilization/embryo transfer program

Purpose This study compares the results of three ovulation induction protocols in polycystic ovarian disease (PCOD) patients undergoing an in vitro fertilizationembryo transfer (IVF-ET) program. A total of 85 cycles was studied. The patients were treated with clomiphene citrate (CC) plus human menopausal gonadotropin (hMG) (CC/hMG group), with purified menofollitropin (pFSH) plus hMG (pFSH/hMG group), and with pFSH/hMG plus gonadotropin releasing hormone analogue (GnRH-a) (analogue group). In the analogue group the suppression of luteinizing hormone (LH) with GnRH-a decreased the number of follicles <12 mm on the day of human chorionic gonadotropin (hCG) administration and the number and percentage of immature oocytes retrieved and increased the percentage of mature oocytes retrieved.Results However, fertilization rates of oocytes, cleaved embryo rates, pregnancy rates following replacement, and pregnancy outcomes were not different.Conclusion Although the suppression of the hypothalamic-pituitary-ovarian axis with GnRH-a in PCOD patients improved follicular synchrony and oocyte maturity, none of the ovulation induction protocols was superior to the others with respect to pregnancy rates and pregnancy outcomes.     

Prospective randomized study of human menotropin versus a follicular and a luteal phase gonadotropin-releasing hormone analog-human menotropin stimulation protocols for in vitro fertilization

OBJECTIVE: To determine whether gonadotropin-releasing hormone analogs (GnRH-a) initiated either in the luteal phase or in the early follicular phase immediately preceding menotropin will improve the fertilization, implantation, and pregnancy rates (PR) in all IVF patients, when compared with menotropins alone. DESIGN: In a prospective, controlled, randomized study we compared a pure follicle-stimulating hormone (FSH) human menopausal gonadotropin (hMG) protocol (group A = control) (n = 93 cycles) to two protocols in which GnRH-a pretreatment plus pure FSH and/or hMG was used in in vitro fertilization candidates. In group B (n = 64) GnRH-a was initiated during the luteal phase and in group C (n = 35) during the follicular phase. RESULTS: We found (1) no differences in fertilization and implantation rates between the three protocols; (2) similar pregnancy rates per transfer when similar number of conceptus were transferred (A = 30%, B = 22%, C = 21%); (3) an increase of the number of oocytes obtained; and (4) a reduction in the cancellation rate with both GnRH-a protocols. CONCLUSIONS: These findings suggest that there is no obvious superiority between the two GnRH-a protocols in the dosage schedule used and that the major advantage of GnRH-a over non-GnRH-a protocols is in decreasing the cancellation rate and increasing the number of oocytes and conceptus obtained. The follicular phase GnRH-a protocol required less hMG-pure FSH than the luteal phase GnRH-a protocol.     

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。     

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.     

Comparison of different stimulation protocols efficacy in poor responders undergoing IVF: A retrospective study

Purpose: To compare the efficacy of different stimulation protocols on pregnancy outcomes in poor responders undergoing in vitro fertilization (IVF). Materials and methods: This was a retrospective study to compare the efficacy of four different protocols including gonadotropin-releasing hormone (GnRH) agonist (long, short and miniflare) and GnRH antagonist on pregnancy outcomes in poor responders. This investigation was performed on 566 poor respond patients who were candidates for IVF. Main outcome measures included the total number of oocytes and mature oocytes retrieved, pregnancy rates, implantation and overall cancellation rates which were compared between four mentioned groups. Results: Number of follicles >18?mm on hCG day were significantly higher in GnRH-a long versus GnRH antagonist, GnRH-a short and GnRH-a miniflare protocols. The mean number of oocytes and mature oocytes retrieved were significantly higher in GnRH-a long versus miniflare (4.7?±?3.05 versus 3.26?±?2.9 and 3.69?±?3.1 versus 2.65?±?2.2, respectively). There were no significant differences in implantation, pregnancy and overall cancellation rates between four groups. Conclusion: The present study suggests that the application of four different protocols in poor respond patients seem to have similar efficacy in improving clinical outcomes such as implantation, pregnancy rates and cancellation rate even though GnRH-a long protocol yielded more retrieved oocytes and mature oocytes compared to GnRH-a miniflare protocol.     

The effect of growth hormone supplementation on in vitro fertilization outcome: a prospective randomized placebo-controlled double-blind study.

OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or placebo were administered in a prospective randomized double-blind manner. PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with mechanical factor infertility and a normal male factor were selected for this study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was initiated in the midluteal phase of the preceding cycle and continued until the day of human chorionic gonadotropin (hCG) administration. Ovulation induction with hMG was started 14 days after pituitary down regulation (17 beta-estradiol [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code at the completion of the study revealed that 20 women received GH and 22 placebo. The age and duration of infertility did not differ between the two groups. Follicular phase duration, hMG ampules used, serum E2, and number of follicles (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and embryos achieved were similar in both groups. Embryo morphology and rate of cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did not change after pituitary down regulation and increased significantly both after GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9% versus 11.3% in the GH and placebo groups, respectively, and were not statistically different. CONCLUSIONS: In normo-ovulatory women undergoing ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary down regulation does not seem to augment ovarian response or improve embryo quality. The effect of this regimen on actual PRs and implantation rates needs further clarification.     

Ovarian hyperstimulation for in vitro fertilization preceded by prolonged administration of a gonadotropin-releasing hormone agonist

In 51 patients, controlled ovarian hyperstimulation with clomiphene citrate (CC)/human menopausal gonadotropin (hMG), or hMG only, in 102 IVF cycles had previously resulted in a cancellation rate of 52% and no pregnancies. In 54 subsequent cycles the women were treated with prolonged administration of a gonadotropin-releasing hormone agonist (GnRHa) followed by hMG stimulation, the GnRHa group. The results were compared with the outcome of 47 cycles in patients who came for their first IVF attempt. In this group a CC/hMG regimen was used, the CC/hMG group. In the GnRHa group, 17 pregnancies were achieved, compared with 10 in the CC/hMG group. Only four cycles were cancelled in the GnRHa group, vis-à-vis 13 in the CC/hMG group, a significant difference. The study showed that prolonged use of GnRHa as a preparatory treatment is effective following previous failures of IVF.     

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。     

Clomiphene citrate and hMG: An alternative stimulation protocol for selected failed in vitro fertilization patients

Purpose This study was carried out to evaluate the potential role of the combination clomiphene citrate/human menopausal gonadotropin (CC/hMG) for patients who failed previous in vitrofertilization (IVF) attempts with gonadotropin-releasing hormone analogs (GnRH- a) and/ or exogenous gonadotropins.Methods Patients were stimulated with CC/hMG (n=93) after unsuccessfully undergoing 182 gonadotropin cycles with (n=106) or without (n=76) luteal-phase GnRH- a. Cancellation rate, length of stimulation, and peak estradiol levels did not differ significantly between the two regimens.Results Although fewer oocytes were retrieved when the CC/hMG combination was used, 16 patients were able to successfully achieve a pregnancy (26.2% delivery rate/ transfer). When daily follicle stimulating hormone (FSH) levels were measured in two successive cycles in those women who conceived with the CC/hMG stimulation, baseline levels did not differ when compared with a previous GnRH-a/hMG cycle. Nevertheless, serum FSH levels rose rapidly and remained higher in the GnRH- a/hMG cycle, reaching significantly higher levels on day of human chorionic gonadotropin (hCG) administration.Conclusion Selected patients who failed previous IVF attempts with gonadotropins with or without GnRH analogs may benefit from the addition of CC to their ovarian stimulation protocol.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

A preliminary study on in vitro fertilization and embryo transfer

Forty-two women with infertility were enrolled in an in vitro fertilization and embryo transfer (IVF/ET) program, from July, 1986 to February, 1988, at the First Affiliated Hospital, Human Medical University. CC/hMG/hCG and hMG/hCG regimens for ovulation induction were used for 35 and 7 patients. Monitoring methods consisted of daily follicular ultrasonography and serum estradiol measurements. Human chorionic gonadotropin 10,000IU was administered when the leading follicle reached 18mm in diameter and serum E2 level was equal to or more than 1,480 pmol/L (400 pg/ml). Twenty-one laparoscopies and nineteen laparotomies for oocyte retrieval were performed. The IVF/ET results using CC/hMG/hCG for ovarian stimulation were as follows: an average of 6.1 follicles were aspirated and 3.5 oocytes recovered for one case. The recovery rate and fertilization rate was 57.0% and 60.1% respectively. In twenty-five women one to five embryos were transferred and a clinical pregnancy occurred in one who received three embryos. Laparotomy for oocyte retrieval showed that more oocytes could be obtained than laparoscopy. The purity of CO2 used for laparoscopy was considered to affect the IVF results.     

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.     

Comparison of ovarian stimulation regimens for in vitro fertilization (IVF) with and without a gonadotropin-releasing hormone (GnRH) agonist: Results of a randomized study

In order to diminish the cancellation rate due to a premature endogeneous LH surge and/or to a poor ovarian response and thus increasing the pregnancy rate, a GnRH agonist (Buserelin) was applied in patients starting their first ovarian stimulation with gonadotropins for IVF. All patients suffered from tubal infertility and were not older than 40 years. Each woman was allocated randomly to one of three groups: the conventional treatment with hMG alone (group I), patients from group II started the hMG treatment shortly after the LH rise caused by the GnRH agonist and patients in group III commenced the hMG treatment when an hypogonadotropic state was achieved after a long treatment of Buserelin. All male partners had a normal spermiogram. A reduction of poor responders to the superovulation is seen in the short-term group (6%), compared with the other two groups (14%). In some cases from group III ovarian cyst formation led to the cancellation of the treatment. The long-term group differs significantly from the other two in the duration of the gonadotropin stimulation and the number of ampoules hMG used. A severe ovarian overstimulation syndrome was not observed. There is no difference in the number of retrieved oocytes and the fertilization rate among the three groups. The pregnancy rate per cycle or per patients in the group with a short-term GnRH-agonist regimen is significantly higher compared to that of the group using the conventional hMG treatment.     

The Effects of Gonadotropin-Releasing Hormone Agonist on Androstenedione Production and Follicular Development During Controlled Ovarian Hyperstimulation

Purpose: We performed a prospective randomized study to assess the effects of a GnRH agonist (GnRH-a) onfollicular development and steroidogenesis during controlled ovarian hyperstimulation (COH). Methods: Patients undergoing in vitro fertilization (IVF)for tubal infertility received human menopausal gonadotropin (hMG) stimulation with or without the GnRH-a, buserelin, beginning in the midluteal phase of the prior cycle. We analyzed serum hormone levels, follicular development, and outcome of IVF. Results: The mean number of retrieved oocytes was significantly greater, and the implantation rate per embryo was significantly higher, in the GnRH-a/hMG group (n = 101) than in the hMG-only group (n = 97). The concentration of androstenedione (A) and the A/estradiol ratio in the serum were significantly lower in the GnRH-a treatment group throughout the follicular phase. Conclusions: The concomitant use of GnRH-a during COH prevents atretic change of the follicles and enhances follicular development by reducing androgen accumulation, resulting in a higher developmental competence of the oocytes.     

Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: a prospective, randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the effect of adjuvant low-dose aspirin on utero-ovarian blood flow and ovarian responsiveness in poor responders undergoing IVF. DESIGN: Prospective randomized, double-blind, placebo-controlled study. SETTING: University-affiliated teaching hospital. PATIENT(S): Sixty patients classified as poor responders undergoing IVF. INTERVENTION(S): Supplementation with low-dose aspirin (80 mg daily) or placebo to a long down-regulation protocol. MAIN OUTCOME MEASURE(S): Doppler measurement of intraovarian and uterine pulsatility index was performed before (baseline) and after ovarian stimulation (day of hCG administration). Duration of use and dose of gonadotropins, cycle cancellation rate, number of mature follicles recruited, and oocytes retrieved were also measured. RESULT(S): High cancellation rates were found in both groups (33.3% vs. 26.7%, placebo vs. treatment). There were no significant differences in total dose of hMG used (66 vs. 57 hMG, 75 IU ampules), median number of mature follicles recruited (3.5 vs. 3.0), or median number of oocytes retrieved (4 vs. 3). No significant differences were found in either intraovarian or uterine artery pulsatility index measured at baseline or on the day of hCG administration. CONCLUSION(S): Supplementation with low-dose aspirin failed to improve either ovarian and uterine blood flow or ovarian responsiveness in poor responders undergoing IVF.