Efficacy of a combined protocol of urinary and recombinant follicle-stimulating hormone used for ovarian stimulation of patients undergoing ICSI cycle

Purpose To evaluate the efficacy of using both urinary and recombinant FSH in a combined protocol for ovarian stimulation in an IVF treatment program. Method A total of 119 infertile couples undergoing ICSI treatment were randomized prospectively in this study. After a standard down-regulation with GnRH analogue, the patients were randomized in 2 groups 58 received combined urinary and recombinant FSH, starting with uFSH and then rFSH, and 61 controls received only recombinant FSH. Result(s) Pregnancy and implantation rates were significantly higher in the combined uFSH/rFSH group than the control (rFSH) group (43.9% vs 22.1% and 27.5% vs 13.2% respectively). Metaphase II oocyte and grade 1 embryos were significantly higher in favour of combined uFSH/rFSH group than the recombinant FSH group. Conclusion(s) This study shows that using a combination of both urinary and recombinant FSH for ovarian stimulation improves oocyte maturity and embryo cleavage, and increases pregnancy and implantation rates.     

Efficacy of recombinant human follicle-stimulating hormone in improving oocyte quality in assisted reproductive techniques

OBJECTIVE: To estimate the efficacy of recombinant human follicle-stimulating hormone (rFSH) versus highly purified urinary human FSH (uFSH) in women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: This prospective, randomized, quality of retrieved double-blind study compared uFSH with rFSH in IVF-ET rFSh cycles. A total of 254 cycles from 241 patients who attended the infertility clinic at Samsung Cheil Hospital from January to August 2001 were included in the study. With pituitary desensitization using gonadotropin-releasing hormone agonist and a short protocol, rFSH was administered in 131 cycles; uFSH was administered in 123 cycles. We analyzed ovarian response, oocyte quality, fertilization rate, embryo quality, pregnancy rate and live birth rate in the uFSH and rFSH groups. RESULTS: Total FSH dosage (1322.3 +/- 526.2 vs. 2124.4 +/- 881.9 i.u.) and dosage per retrieved oocyte (90.6 +/- 36.0 vs. 138.0 +/- 57.2 i.u.) were significantly lower in the rFSH group than those in the uFSH group (P < .001). The proportion of good-quality oocytes (grade 1 and 2) was higher in the rFSH group (68.2% vs. 64.8%, P = .024). Moreover, the proportion of atretic oocytes (grade 5) was lower in the rFSH group (7.5% vs. 10.3%, P = .002). The fertilization rate, quality of transferred embryos, clinical pregnancy rate and live birth rate were not significantly differ between the 2 groups. CONCLUSION: In women undergoing COH, rFSH revealed more efficient ovarian response and better quality of oocytes than did uFSH.     

Effectiveness of human menopausal gonadotropin versus recombinant follicle-stimulating hormone for controlled ovarian hyperstimulation in assisted reproductive cycles: a meta-analysis

OBJECTIVE: To compare the effectiveness of hMG and recombinant FSH after down-regulation for ovulation stimulation in assisted reproductive cycles. DESIGN: Meta-analysis. SETTING: Infertility centers providing assisted reproductive techniques. PATIENT(S): Two thousand thirty women undergoing IVF or ICSI. INTERVENTIONS: Ovarian hyperstimulation with hMG or recombinant FSH after down-regulation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, ongoing pregnancy/live birth rate, gonadotropin dose used, oocytes retrieved, implantation rate, miscarriage rate, and multiple pregnancy rate. RESULT(S): Six randomized controlled trials were included. In all trials, the group of women treated with hMG had higher pregnancy rates. Pooling the five trials that used a long GnRH agonist protocol resulted in a higher clinical pregnancy rate for hMG compared with recombinant FSH (relative risk, 1.22 [95% CI, 1.03 to 1.44]). However, there was no evidence of a difference in rates of ongoing pregnancy or live birth per woman between hMG recipients and recombinant FSH recipients (relative risk, 1.20 [95% CI, 0.99 to 1.45]). No differences were found in gonadotropin dose used, oocytes retrieved, miscarriage rate, or multiple pregnancy rate. CONCLUSION(S): Use of hMG resulted in higher clinical pregnancy rates than did use of recombinant FSH in IVF/ICSI cycles after GnRH agonist down-regulation in a long protocol.     

The use of a starting dose of recombinant follicle stimulating hormone for controlled ovarian hyperstimulation: a randomized pilot study

The aim of this study was to compare the costs and effects of two different controlled ovarian hyperstimulation treatments: a starting dose of recombinant follicle stimulating hormone (FSH) followed by highly purified urinary FSH; or highly purified urinary FSH alone.

Forty-six infertile patients, after being given luteal gonadotropin-releasing hormone (GnRH) agonist, were randomly assigned to the two stimulation protocols. During the ovarian stimulation regimen the patients underwent transvaginal ultrasonographic evaluation of follicular number and size. The retrieved oocytes were classified on the basis of the criteria of Acosta and colleagues. To study the impact of embryo quality on implantation, the embryos were graded morphologically before replacement. Pregnancy rates were ascertained and the costs of the two different protocols were analyzed.

The number of days of FSH stimulation and the cost of gonadotropin treatment were similar in both groups. The number of follicles > 17 mm in size, the number of collected oocytes, and pregnancy rate per cycle were significantly higher in the group partially treated with recombinant gonadotropin. We conclude from these results that the use of recombinant FSH in the early phase of controlled ovarian hyperstimulation leads to significant improvements in pregnancy rate per cycle without increasing the costs of treatment.     

Evaluation of mixed protocols with Bravelle (human-derived FSH) and Repronex (hMG) to assess clinical efficacy (EMBRACE) in women undergoing in vitro fertilization

OBJECTIVE: To compare the efficacy and safety of three different ratios of human-derived follicle-stimulating hormone/human menopausal gonadotropin (human-derived FSH:hMG, Bravelle and Repronex) mixed together in the same syringe and administered subcutaneously once daily, to in vitro fertilization (IVF) patients <34 years or 34 to 40 years of age. DESIGN: Two randomized, prospective, age stratified, IVF studies. SETTING: Twenty-one academic and private clinics with experience in IVF/embryo transfer (ET). PATIENT(S): Infertile premenopausal women undergoing IVF-ET. INTERVENTION(S): Pituitary suppression with leuprolide acetate, randomization to one of three treatment groups, followed by gonadotropin stimulation (GS) for up to 15 days. The human-derived FSH:hMG ratios were the following: Group 1, a 1:1 ratio throughout; Group 2, a 3:0 ratio that was changed to 1:1 after GS day 5; Group 3, a 2:1 ratio that was increased to 3:1, 4:1, or 5:1 after GS day 5, as needed. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved; peak estradiol levels; dose and duration of stimulation; implantation rates; adverse events; injection site pain; and pregnancy and live birth rates. RESULT(S): Overall, women <34 years had higher E(2) levels, more oocytes retrieved, and improved implantation and live birth rates compared with women 34 to 40 years old. Nonetheless, each ratio of human-derived FSH:hMG produced comparable implantation rates, and continuing pregnancy and take-home baby rates. CONCLUSION(S): All three ratios of human-derived FSH:hMG in both age groups produced comparable pregnancy and live birth rates with similar safety results.     

Elevated basal FSH and embryo quality: lessons from extended culture embryos

Background  The relationship between elevated basal FSH and embryo quality remains a topic of heated discussion among practitioners of ART. Some authors suggest a negative effect of raised FSH on the quality of embryos and therefore on IVF treatment outcome. We postulate that women with elevated FSH who respond well to ovarian stimulation and have embryos to transfer, have the same chance of conceiving like women of a similar age with normal FSH. To test this hypothesis, we studied women with elevated basal FSH who made enough embryos to qualify for blastocyst culture and day 5 embryo transfer. Methods  Analysis of data collected prospectively, on women age 25–43 years, who underwent IVF between January 2005 and December 2006. The women were divided into: those with high FSH (≥10 IU/L) and women with normal FSH (<10 IU/L). We analysed data to show treatment outcome in the two groups, following embryo transfer on day 3 and after transfer on day 5. Outcome measures include number of oocytes retrieved, number of embryos available, implantation rate, pregnancy and live birth rate. Results  Among the 1,858 women who under-went a day 3 transfer, 1,368 had basal FSH ≤ 10 IU/L, and in 492 basal FSH was above 10 IU/L. The average number of oocytes retrieved was lower among women with elevated FSH (10.12 ± 5.6 Vs 6.16 ± 3.9). Women with a normal FSH, had a higher pregnant and live birth rate than those with elevated FSH (43.3% vs 27.9% p = 0.021) and (30.8% vs 17.6% p = 0.028) respectively. 398 women made enough embryos to qualify for extended embryo culture to blastocysts. Of these 366 had an FSH ≤ 10 IU/L and 32 had FSH > 10 IU/L. In this group, there was no significant difference in the pregnancy and live birth rates between women with elevated and those with normal FSH, (67.2% vs 65.6%) and (51.9% vs 43.8%) respectively. In this selected group of women where quantity is not an issue, the quality of embryos was same irrespective of whether the basal FSH was low or high. Conclusion  Women with elevated basal FSH who respond well to stimulation and generate a good number of oocytes / embryos have a chance of becoming pregnant and having a live birth similar to that of women of their age. Women should therefore not be denied the benefits of IVF based solely on the basal FSH level as a subset may respond well and therefore have a good chance of taking home a baby.     

A comparison of 3-day and daily follicle-stimulating hormone injections on stimulation days 1-6 in women undergoing controlled ovarian hyperstimulation

OBJECTIVE: To evaluate the efficacy of ovarian hyperstimulation by intermittent doses of 450 IU of recombinant human (h)FSH compared with daily 150-IU doses of recombinant hFSH. DESIGN: A pilot, open, randomized, parallel-group study. SETTING: Center for Reproductive Medicine, Düsseldorf, Germany. PATIENT(S): Infertile women with indication for IVF/intracytoplasmic sperm injection after at least 1 year of unprotected intercourse. INTERVENTION(S): Recombinant hFSH was administered daily or intermittently (3-day intervals) from days 1 to 6 of stimulation and thereafter by daily injection. MAIN OUTCOME MEASURE(S): Number of preovulatory follicles, retrieved oocytes, two-pronuclei (2PN) zygotes, implantation, and pregnancy rates. RESULT(S): The number of oocytes in the daily-dose group was significantly greater. There were no significant differences in mean values for number of follicles > or =11 mm (except for day 7) and > or =14 mm, 2PN zygotes, and number of transferred embryos. Implantation and pregnancy rates per cycle were in favor of the intermittent 450-IU dose regimen; implantation rates were 17.0% and 9.8% in the 3-day-dose and daily-dose groups, respectively, and biochemical and clinical pregnancy rates were 33.3% and 15.7% and 25.5% and 13.7%, respectively. CONCLUSION(S): Intermittent administration of recombinant hFSH significantly reduces the total number of recombinant hFSH injections, compared with a conventional FSH regimen, without detrimental effects on implantation rate or pregnancy rate.     

Recombinant gonadotrophins associated with GnRH antagonist (cetrorelix) in ovarian stimulation for ICSI: comparison of r-FSH alone and in combination with r-LH

OBJECTIVE: The objective was to verify the outcome of intracytoplasmic sperm injection (ICSI) with ovulation induction performed with GnRH antagonists, comparing the use of recombinant follicle-stimulating hormone (r-FSH) alone and in combination with recombinant luteinizing hormone (r-LH) in a prospective and randomized trial. STUDY DESIGN: Forty male-factor infertile normo-ovulatory patients undergoing ovarian stimulation for ICSI took part in the study. After initiating ovarian stimulation with only r-FSH, all patients were treated with GnRH antagonist (cetrorelix). When beginning cetrorelix administration, the patients were randomized into two groups: in group I, 20 patients continued to receive r-FSH alone and in group II, 20 patients received combined r-FSH and r-LH. The number of metaphase II oocytes, estradiol concentration at the time of hCG administration, fertilization rate, grade 1 embryo rate, pregnancy rate per cycle, and implantation rate were measured. Results are expressed as mean+/-S.D. RESULTS: In group I, the women's age was 32.3+/-2.30 years, and FSH concentration was 7.8+/-1.7 IU/ml. In group II, the women's age was 32.2+/-2.46 years and FSH concentration was 7.5+/-1.7 IU/ml. The number of oocytes retrieved was 9.6+/-2.9 and the number of metaphase II oocytes was 6.7+/-2.2 in group I. In group II the number of retrieved oocytes were 9.9+/-2.6 and the number of metaphase II oocytes 6.9+/-2.1 (p>0.05). Estradiol concentration at the time of hCG was 4.6+/-1.8 nm/l in group I and 6.7+/-2.0 nm/l in group II (p<0.01). Fertilization rate was 73.0% in group I versus 78.2% in group II. In group I, we obtained 53.9% of grade 1 embryos versus 54.4% in group II (p>0.05). Pregnancy and implantation rates in group I were 30.0 and 16.7%, respectively and in group II 35.0 and 20.4%, respectively (p>0.05). CONCLUSIONS: The use of recombinant LH in addition to recombinant FSH may prevent a decrease in estradiol after GnRH antagonist administration, but does not influence positively the outcome of oocyte number, maturation, embryo quality, fertilization rate, pregnancy rate per cycle, and implantation rate.     

The use of a starting dose of recombinant follicle stimulating hormone for controlled ovarian hyperstimulation: a randomized pilot study.

The aim of this study was to compare the costs and effects of two different controlled ovarian hyperstimulation treatments: a starting dose of recombinant follicle stimulating hormone (FSH) followed by highly purified urinary FSH; or highly purified urinary FSH alone. Forty-six infertile patients, after being given luteal gonadotropin-releasing hormone (GnRH) agonist, were randomly assigned to the two stimulation protocols. During the ovarian stimulation regimen the patients underwent transvaginal ultrasonographic evaluation of follicular number and size. The retrieved oocytes were classified on the basis of the criteria of Acosta and colleagues. To study the impact of embryo quality on implantation, the embryos were graded morphologically before replacement. Pregnancy rates were ascertained and the costs of the two different protocols were analyzed. The number of days of FSH stimulation and the cost of gonadotropin treatment were similar in both groups. The number of follicles > 17 mm in size, the number of collected oocytes, and pregnancy rate per cycle were significantly higher in the group partially treated with recombinant gonadotropin. We conclude from these results that the use of recombinant FSH in the early phase of controlled ovarian hyperstimulation leads to significant improvements in pregnancy rate per cycle without increasing the costs of treatment.     

A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment

OBJECTIVE: To compare fixed daily doses of the recombinant FSH (rFSH) Gonal-F (150 IU vs. 225 IU) for ovarian stimulation in IVF-ET. DESIGN: Single-center prospective, randomized study. Assisted conception unit of a university hospital.One hundred twenty-four women aged 23-41 years participated in the study. Exclusion criteria were as follows: FSH of >10 IU/L, polycystic ovarian syndrome, one ovary or previous ovarian surgery, previous poor response to ovarian stimulation, or ovarian hyperstimulation syndrome (OHSS). INTERVENTION(S): Randomized to commence 150 IU or 225 IU of Gonal-F per day without dose alterations during treatment. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved and total rFSH dose. RESULT(S): More oocytes were retrieved in women aged or=33 years), the number of oocytes retrieved in the two groups were similar. No significant differences were found for fertilization rate, number of embryos formed and cryopreserved, and pregnancy rates between the two groups. The total rFSH dose used was higher in the 225-IU group (2,595.0 +/- 510.0 vs. 1,897.5 +/- 457.5 IU). The cancellation rate due to insufficient ovarian response was higher in the 150-IU group (15.0% vs. 3.3%). All cases of ovarian hyperstimulation syndrome (n = 4) occurred in the 225-IU group. CONCLUSION(S): Two hundred twenty-five IU is more effective than 150 IU in younger women but requires a higher total dose of Gonal-F. The use of 225 IU in older women did not result in a higher oocyte yield, suggesting that 225 IU of rFSH does not compensate for the age-related decline in the number of follicles available for stimulation.     

Recombinant versus urinary follicle-stimulating hormone in intrauterine insemination cycles: a prospective, randomized analysis of cost effectiveness

OBJECTIVE: To compare the clinical results and the cost effectiveness of urinary FSH and recombinant FSH in ovarian stimulation for IUI cycles. DESIGN: Prospective, randomized trial. SETTING: University Hospital, Perugia, and A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy. PATIENT(S): IUI cycles were performed in 67 infertile patients. INTERVENTION(S): Protocols of ovarian stimulation with urinary FSH or recombinant FSH were randomly assigned, for a total of 138 cycles performed (67 and 71, respectively). MAIN OUTCOME MEASURE(S): Number of mature follicles, days of stimulation, number of ampules, and IU used per cycle, biochemical/clinical pregnancy rates and cost-effectiveness ratio. RESULT(S): Follicular development, length of stimulation, pregnancy and delivery rates were not statistically different. Although in the urinary FSH group a significantly higher number of IU of gonadotropins were used (815.5 +/- 284.9 vs. 596.0 +/- 253.8), the cost per cycle remained significantly lower (220.73 +/- 94.72 vs. 318.50 +/- 125.21). The cost-effectiveness ratio was 1,848.61 euro in the urinary FSH group and 2,512.61 euro in the recombinant FSH group. CONCLUSION(S): Urinary FSH and recombinant FSH are both effective in ovarian stimulation in IUI cycles. The urinary preparation is more cost effective due to the difference of its cost per IU.     

Exogenous luteinizing hormone in controlled ovarian hyperstimulation for assisted reproduction techniques

OBJECTIVE: To investigate the role of exogenous LH in controlled ovarian hyperstimulation for assisted reproductive technologies. DESIGN: Prospective randomized study. SETTING: SISMER fertility unit. PATIENT(S): Women showing a hyporesponsiveness to FSH under GnRH agonist down-regulation were randomized into three groups: group A (n = 54) received an increased dosage of FSH; group B (n = 54) was administered recombinant LH in addition to the increased dose of FSH; group C (n = 22) was given additional FSH and LH using hMG as a combined drug. Fifty-four age-matched women with no need to increase the FSH dose were included as a control group (D). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation and live birth rate per started cycles. RESULT(S): In group B, the pregnancy and implantation rates were statistically higher when compared with groups A and C and did not differ from the control group for normal response. The live birth rate was similar in groups B and D but was half as high in groups A and C. CONCLUSION(S): Hyporesponsiveness to FSH could be related to iatrogenic LH deficiency that, in turn, could affect oocyte competence. Addition of a small amount of recombinant LH is able to rescue oocyte competence to produce viable embryos.     

Embryo quality based on ovulation induction: defining the differences

Patients undergoing IVF, with or without intracytoplasmic sperm injection, were treated with either recombinant human FSH or urine-derived FSH. Response to ovarian stimulation was monitored by ultrasound examinations and measurement of serum oestradiol concentrations. To define any differences in embryo quality and hence assisted reproductive technology success rates, a retrospective analysis of 811 recombinant FSH versus 555 urinary FSH cycles was undertaken. Embryo quality was assessed as embryo cell number and degree of fragmentation. Implantation and ongoing pregnancy rates were also compared. Use of recombinant FSH resulted in a higher percentage of mature oocytes, improved embryo cleavage, with more embryos available for freezing and higher implantation rates compared with urinary FSH. Oocyte and embryo quality were superior when recombinant FSH was used for ovarian stimulation compared with urinary FSH.     

Follitropin-alpha versus human menopausal gonadotropin in an in vitro fertilization program

OBJECTIVE: To compare the efficacy of recombinant FSH and urinary-derived hMG for ovarian stimulation during IVF. DESIGN: Retrospective analysis of data from IVF cycles conducted over 15 months. SETTING: University hospital IVF unit. PATIENT(S): Three hundred twenty-four women undergoing their first to sixth IVF cycle. INTERVENTION(S): After pituitary down-regulation, patients received recombinant FSH or hMG, according to personal choice. After hCG administration, patients underwent oocyte retrieval, oocyte fertilization, and embryo transfer. MAIN OUTCOME MEASURE(S): Implantation rate and clinical ongoing pregnancy rate per oocyte retrieval. RESULT(S): Patients who chose recombinant FSH were slightly younger than those who chose hMG (34.1 vs. 35.1 years, respectively). Although more embryos were transferred in the hMG group (3.6 vs. 3.2), the ongoing pregnancy and implantation rates were significantly higher in the recombinant FSH group (ongoing pregnancy rate, 50.0% vs. 36.2%). CONCLUSION(S): Recombinant FSH is more effective than hMG for ovarian stimulation in IVF cycles. This increased efficacy, which is achieved with fewer ampoules, is likely to offset the higher acquisition costs of recombinant FSH.     

First live birth after ovarian stimulation using a chimeric long-acting human recombinant follicle-stimulating hormone (FSH) agonist (recFSH-CTP) for in vitro fertilization

OBJECTIVE: To report the first pregnancy and live birth after ovarian stimulation using a chimeric long-acting human recombinant FSH agonist (recFSH-CTP) for IVF. DESIGN: Case report. SETTING: Tertiary fertility center. PATIENT(S): A 32-year-old woman with a 7-year history of primary infertility. INTERVENTION(S): Ovarian stimulation with a single SC injection of 180 microg recFSH-CTP on cycle day 3, followed by daily injections of 150 IU recFSH from cycle day 10 onward, combined with daily GnRH antagonist 0.25 mg SC to prevent a premature LH rise. Final oocyte maturation was induced by 10,000 IU hCG. MAIN OUTCOME MEASURE(S): First ongoing pregnancy obtained with recFSH-CTP. RESULT(S): Twelve oocytes were retrieved. Ten oocytes were fertilized in vitro by intracytoplasmic sperm injection, and from these 10 oocytes, two embryos were subsequently transferred after 3 days of culture. A pregnancy test 2 weeks after ET was positive, and ultrasound investigation revealed an intact, intrauterine, singleton pregnancy after 12 weeks. CONCLUSION(S): The first pregnancy and live birth was achieved after ovarian stimulation using recFSH-CTP for IVF.     

Should cryopreserved epididymal or testicular sperm be recovered from obstructive azoospermic men for ICSI?

OBJECTIVE: To determine the effect of the anatomical site of sperm recovery on intracytoplasmic sperm injection (ICSI) embryo implantation, pregnancy and live birth rates in couples with isolated obstructive azoospermia as the sole cause of infertility. DESIGN: Controlled, single centre, retrospective clinical study. SETTING: University Hospital, Centre for Reproductive Medicine. SAMPLE: One hundred and fifty-one cycles of ICSI were performed, using surgically recovered sperm, between August 1996 and March 2002. METHODS: The outcome of ICSI, with surgically recovered sperm, was compared between epididymal (Group E) and testicular (Group T) derived sperm. Inclusion was limited to couples undergoing their first treatment cycle, where female age was < or =39 years and a minimum of five oocytes were available for injection. Women with a history of ovarian surgery, ultrasonic evidence of polycystic ovaries, uterine anomalies or hydrosalpinx were excluded. MAIN OUTCOME MEASURES: Clinical pregnancy, implantation and live birth rate. RESULTS: Forty-two of 151 cycles met the strict inclusion criteria. Groups E and T were comparable with respect to age, basal serum FSH, ovarian response; number of oocytes injected and number of embryos available and transferred. No difference existed between Groups E and T in implantation, clinical pregnancy or live birth rate (28.8% vs 25.8%, 42.9% vs 42.9% and 39.3% vs 42.9%, respectively). CONCLUSIONS: Cryopreserved epididymal and testicular sperm, from men with obstructive azoospermia, appear equally effective in ICSI. Epididymal recovery should remain the method of first choice for obstructive azoospermic men but further study of sperm DNA damage rates in different testicular sites is required.     

Follicle-stimulating hormone and estradiol levels independently predict the success of assisted reproductive technology treatment

OBJECTIVE: To evaluate the relationship between early follicular phase levels of FSH and E(2) and outcomes of therapy with assisted reproductive technologies (ART). DESIGN: Retrospective cohort study. SETTING: ART centers in the United States. PATIENT(S): Women receiving 19,682 ART procedures performed in 135 clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of clinical pregnancy, live birth delivery, and high ovarian response (>/=10 oocytes retrieved after stimulation). RESULT(S): The ratio of each FSH or E(2) value to the respective upper limit of normal value for the clinic was computed. Within each age group, rates of pregnancy, live birth, and high ovarian response decreased linearly as FSH levels increased. For example, among women 35 years of age and younger, pregnancy rates (PR) ranged from 41.1% (FSH ratio 0-0.5) to 18.5% (FSH ratio >2.0). The three outcomes exhibited a similar downward trend as E(2) ratios increased. When both hormone ratios were elevated, outcomes were least favorable. These relationships remained statistically significant after we adjusted for diagnosis, number of embryos transferred, previous births, previous ART therapy, and use of GIFT, zygote intrafallopian transfer (ZIFT), intracytoplasmic sperm injection (ICSI), or assisted hatching. CONCLUSION(S): The FSH and E(2) ratios predict ART success independent of age and other clinical prognostic factors.     

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。     

Clinical experience with recombinant follicle-stimulating hormone (FSH) and urinary FSH: a retrospective case- controlled analysis

OBJECTIVE: To compare the efficacy and efficiency of recombinant FSH (rFSH) and urinary FSH (uFSH). DESIGN: Retrospective case controlled analysis. SETTING: An assisted reproduction unit at a university center. PATIENT(S): 1388 patients undergoing long protocol in vitro fertilization/embryo transfer (IVF-ET) using buserelin acetate from day 2 of the cycle and either rFSH (follitropin beta) (n = 694) or uFSH (n = 694) with equal number of ampules started (rFSH: 50 IU, uFSH: 75 IU). INTERVENTION(S): Patients were included in the two groups of treatment after matching for similarity in age and type of treatment (IVF or intracytoplasmic sperm injection). MAIN OUTCOME MEASURE(S): Total dose of FSH, ovarian response, and IVF outcome. RESULT(S): Patients who received uFSH experienced a shorter period of stimulation, and a higher number of oocytes were collected. The total FSH used was lower in the rFSH group, and they required a lower FSH dose per oocyte retrieved. The implantation and pregnancy rates were similar between the uFSH and rFSH groups. In both groups implantation and pregnancy rates were higher when intracytoplasmic sperm injection was performed as compared with IVF. CONCLUSION(S): The implantation and pregnancy rates are similar when either rFSH or uFSH is used (when compared on an ampule-to-ampule basis, rFSH: 50 IU, and uFSH: 75 IU). However, a significantly lower total FSH dose was used in the rFSH group with a lower FSH dose per oocyte collected.     

Prospective randomized study of two cryopreservation policies avoiding embryo selection: the pronucleate stage leads to a higher cumulative delivery rate than the early cleavage stage

OBJECTIVE: To compare the cumulative live birth rates obtained after cryopreservation of either pronucleate (PN) zygotes or early-cleavage (EC) embryos. DESIGN: Prospective randomized study. SETTING: University hospital. PATIENT(S): Three hundred eighty-two patients, involved in an IVF/ICSI program from January 1993 to December 1995, who had their supernumerary embryos cryopreserved either at the PN (group I) or EC (group II) stage. For 89 patients, cryopreservation of EC embryos was canceled because of poor embryo development (group III). Frozen-thawed embryo transfers performed up to December 1998 were considered. MAIN OUTCOME MEASURE(S): Age, oocytes, zygotes, cryopreserved and transferred embryos, damage after thawing, cumulative embryo scores, implantation, and cumulative live birth rates. RESULT(S): The clinical pregnancy and live birth rates were similar in all groups after fresh embryo transfers. Significantly higher implantation (10.5% vs. 5.9%) and pregnancy rates (19.5% vs. 10.9%; P< or = .02 per transfer after cryopreserved embryo transfers were obtained in group I versus group II, leading to higher cumulative pregnancy (55.5% vs. 38.6%; P < or = .002 and live birth rates (46.9% vs. 27.7%; P< or = .0001.Conclusion(s): The transfer of a maximum of three unselected embryos and freezing of all supernumerary PN zygotes can be safely done with significantly higher cumulative pregnancy chances than cryopreserving at a later EC stage.