Concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid and serum in relation to stimulation protocol and outcome of assisted reproduction treatment

In this prospective, randomized study, concentrations of gonadotrophins and steroids in pre-ovulatory follicular fluid (FF) and serum were related to type of stimulation protocol as well as to the outcome of assisted reproduction in 280 women subjected to the long protocol gonadotrophin-releasing hormone (GnRH) agonist pituitary down-regulation and ovarian stimulation with either human menopausal gonadotrophin (HMG) or recombinant FSH. In the women treated with HMG, concentrations of LH, FSH, oestradiol and androstenedione in FF were significantly higher, and those of human chorionic gonadotrophin (HCG) and progesterone significantly lower, than in the women treated with recombinant FSH (rFSH). More women became pregnant and delivered in the HMG than in the rFSH group. These differences, however, were not statistically significant. Concentrations of FSH in serum and of FSH and LH in FF were significantly higher in conception than in non-conception cycles, whereas all other hormone concentrations in FF and serum were similar. The present study demonstrates that the pre-ovulatory follicular fluid hormone profile is significantly influenced by the gonadotrophin preparation used for ovarian stimulation, and suggests that ovarian stimulation with HMG results in an intra-follicular hormone profile more similar to that characterizing conception cycles than stimulation with rFSH. However, as the present data represent means of FF hormone profiles, they do not allow the conclusion of a direct correlation between the intra-follicular concentration of a certain hormone and the ability of the corresponding embryo to implant and establish an ongoing pregnancy.     

Leptin,VEGF, IGF-1, and IGFBP-3 concentrations in serum and follicular fluid of women undergoing in vitro fertilization

We studied the influence of recombinant follicle-stimulating hormone (rFSH) stimulation on the concentration of leptin, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum and follicular fluid (FF) in women undergoing assisted reproduction. To test the hypothesis that these hormones could predict successful implantation and that the levels correlate with pregnancy rate. Sequential serum samples were drawn at the beginning of stimulation and on the day of embryo transfer (ET) from 84 women undergoing IVF. The follicular fluid (FF) obtained during oocyte retrieval was collected and the concentration of leptin, VEGF, IGF-1 and IGFBP-3 were measured in all samples. The hormones were measured by commercially available IRMA, RIA or EIA. Patients' characteristics and results of the assisted reproductive cycles were registered. Serum concentrations of VEGF, IGF-1 and IGFBP-3 significantly decreased during rFSH treatment. In contrast, serum leptin significantly increased after rFSH treatment. A strong correlation was found between the FF - levels of IGF-1, IGFBP-3, leptin and respective serum levels. With regard to IVF outcome, higher serum concentrations of IGF-1, IGFBP-3 and VEGF on the day of oocyte retrieval were observed in conception cycles vs. non-conception cycles. No such difference, however, was apparent at the beginning of the stimulation cycle. There was no association between FF levels of any of these hormones and IVF outcome. Our results demonstrate that VEGF, IGF-1, IGFBP-3 and leptin levels are affected by rFSH during controlled ovarian hyperstimulation and that there is a direct association between serum and FF levels, albeit without clinical implications     

Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles

The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles. An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using the likelihood ratio test in a logistic regression analysis. The live birth rate per cycle initiated was 26.5% (130/491) with HP-HMG and 20.8% (103/495) with rFSH (P = 0.041). The odds ratio in favour of HP-HMG was 1.36 (95% confidence interval: 1.01-1.83). Thus, the findings of this integrated analysis demonstrate that ovarian stimulation with HP-HMG, following a long down-regulation protocol, in IVF cycles results in significantly more live births than stimulation with rFSH alone.     

Protocol of GNRH antagonist in poor responders in IVF-ET cycles

INTRODUCTION: Response to stimulation is one of the factors that affect the results of infertility treatment in IVF-ET cycles. Poor responders as well as the occurrence of ovulation prior to the oocyte retrieval is a main reason of nearly 30% of cancellations of the treatment cycles. In poor responders high doses of gonadotrophins are sometimes required. However administration of gonadotrophins alone does not prevent premature LH surge. The aim of the study was to assess controlled ovarian stimulation protocols with GnRH antagonists (Cetrotide) in poor responders. MATERIAL AND METHODS: The study group consisted of 27 infertile women, mean age 35.8 (range 28-45) undergoing the second IVF cycle. In those women the first cycle was either cancelled due to the lack of follicles' development or the small number of growing follicles (1-2). Ovarian stimulation was started on the 2 day of cycle with administration of 225 IU or rFSH or hMG. Cetrotide was administered subcutaneously in a daily dose of 0.25 mg starting when estradiol serum concentration reached 150 pg/ml with a lead follicle 14 mm diameter and continued throughout the gonadotrophin treatment until HCG administration. RESULTS: In 31 cycles the mean number of MII oocytes retrieved was 4.71 (range 1-10). In one woman there was no mature oocytes obtained during pick-up. In one case the cycle was cancelled due to the bad response. The mean duration of cetrotide administration was 5.16 days. The mean number of rFSH and HMG ampoules was 23 and 30 respectively. The fertilisation rate was 64%. Embryo transfer was performed on the 3rd day after pick-up. The pregnancy rate in this group was 22%. There weren't any adverse effects of Cetrotide in treated women. No case of ovarian hyperstimulation syndrome occurred. CONCLUSION: Ovarian stimulation protocol with GnRH antagonist is effective in poor responders in IVF-ET cycles.     

卵泡刺激素刺激后血清抑制素B和雌二醇预测体外受精周期中卵巢的反应性及其相关性

目的 探讨以经重组卵泡刺激素（rFSH）刺激后体外受精（IVF）周期中不同时间血清抑制素B（INHB）、雌二醇（E2）的动态变化,预测不孕患者卵巢的反应性,为选择最佳的超促排卵方案提供理论依据。方法 采用酶联免疫吸附试验,测定57例不孕患者（年龄〈40岁）于IVF周期中的不同时问,即月经第3天、注射rFSH前、注射rFSH后1d,及注射rFSH后5d的血清INHB、E2水平,并与反映卵巢反应性的2个指标——获卵数／rFSH总量、（卵泡数／rFSH总量）的平方根进行相关性分析。根据本研究中卵泡数及获卵数、是否发生卵巢过度刺激综合征（OHSS）的情况,将57例患者分为低反应组、过度刺激组及正常反应组,比较3组注射rFSH后INHB及E2水平的变化。结果 （1）注射rFSH后1、5d,其血清INHB及E：水平均与卵巢反应性呈显著正相关（INHB：rS=0．69—0．73,E2：rS=0．60～0．73;P=0．000）。（2）低反应组、正常反应组及过度刺激组注射rFSH后5d,患者血清INHB水平分别为164．7、696．2及1263．5ng／L,E2水平分别为303．2、1709．5及4261．0pmol／L,低反应组明显低于正常反应组,正常反应组明显低于过度刺激组,3组分别比较,差异均有统计学意义（P（0．01）。结论 经rFSH刺激后,血清INHB及E2水平能较敏感地预测卵巢对rFSH刺激的反应性,且INHB比E2更敏感。INHB及E2水平降低,可预测卵巢的低反应性;反之,可预测发生OHSS。     

Enhanced oestradiol secretion briefly after embryo transfer in conception cycles from IVF

The hypothesis was tested that conception cycles (CC) resulting from IVF can be distinguished from non-conception cycles (NC) by differences in corpora lutea function that are detectable at the earliest stage of embryo implantation. Luteal oestradiol secretion was analysed retrospectively in 409 ovarian stimulation cycles of 296 patients from the day of embryo transfer until 14 days after embryo transfer (ET+14) in IVF/intracytoplasmic sperm injection (ICSI) cycles. Human chorionic gonadotrophin (HCG) was administered in 330 of 409 cycles in addition to vaginal progesterone in all cycles. Differences in serum oestradiol concentrations between CC and NC increased from day ET+1 onward and became statistically significant on days ET+4 through ET+14, with higher oestradiol concentrations in CC compared with NC. Even though exogenous HCG administration prevented the fall in luteal oestradiol concentrations after ET+4 both in CC and NC, increasing differences in oestradiol concentrations between CC and NC after embryo transfer were observed in both groups of HCG-supplemented and non-supplemented cycles. It is concluded that luteal oestradiol secretion is affected at the earliest stage of embryo implantation. The putative early signal to the corpus luteum associated with embryo attachment and early implantation appears to be superimposed onto the effect of exogenous luteal HCG administration and is clearly distinguishable as early as 4 days after embryo transfer in conception cycles.     

Double GnRH-antagonist dose before HCG administration may prevent OHSS in oocyte-donor cycles: a pilot study

This pilot study evaluated the possibility of preventing early ovarian hyperstimulation syndrome (OHSS) by increasing the daily dose of gonadotrophin-releasing hormone (GnRH) antagonist administration (to twice a day) in oocyte-donor cycles stimulated with the antagonist protocol. The study included 72 oocyte donors who underwent ovarian stimulation using the GnRH antagonist protocol and might have had their cycle cancelled because of ovarian hyper-response. All women were donors presenting a rapid rise of oestradiol ?3000 pg/ml early in the stimulation period with more than 15 follicles of ?15 mm in diameter. By decreasing the rFSH dose to 75 IU a day with an additional daily dose of GnRH antagonist (0.25 mg twice a day), the oestradiol concentrations were lowered or reached a plateau before human chorionic gonadotrophin was given. A marked decrease in oestradiol concentrations and ovarian volume was observed on the day of oocyte retrieval and 3 days post retrieval. None of the donors needed coasting, were cancelled or developed OHSS. In over-responding oocyte donors, by increasing the usual GnRH-antagonist dose to twice a day during ovarian stimulation, the oestradiol rise can be blocked while a minimal follicular stimulation may continue without the risk of developing OHSS or affecting the outcome.This study was conducted in order to investigate whether GnRH antagonist (Ganirelix) may prevent the early OHSS by doubling the daily dose in oocyte donor cycles stimulated with the antagonist protocol. Seventy two oocyte donors at high risk for OHSS were included in the study that might have their cycle cancelled because of ovarian hyperesponse. All cases were donors presenting significantly elevated or rapidly rising serum estradiol levels E2 ? 3000 pg/ml with more than 15 follicles none of which had the appropriate diameter to be considered mature for triggering ovulation. By decreasing the rFSH dose to 75IU a day with an additional daily dose of GnRH antagonist (0.25 twice a day) the estradiol levels were lowered or reached a plateau before the hCG was given. A marked decrease of estradiol levels and ovarian volume was observed the day of oocyte retrieval and three days post retrieval. None of the donors needed coasting, were cancelled or developed OHSS.In conclusion, in oocyte donors at high risk for OHSS, by increasing to twice a day the usual GnRH-antagonist dose one or two days before hCG administration, the estradiol rise could be blocked while a minimal follicular stimulation may continue without the risk of developing OHSS or affecting the outcome.     

减少GnRHa剂量对长方案促排卵卵巢反应性的影响

目的:探讨减少GnRHa剂量对长方案促排卵的卵巢反应性影响。方法:对37例采用长方案进行促排卵且第一周期未妊娠或流产的患者进行自身对照研究,第一个周期GnRHa用量为0.05mg/d,第二个周期GnRHa用量为0.03mg/d。结果:Gn使用天数、Gn用量、受精率第一、第二促排卵周期间无显著性差异(P>0.05)。获卵数、可移植胚胎数第二周期组较第一周期组显著增加(P<0.05)。结论:本研究认为在长方案促排卵过程中减少GnRHa的剂量可以增加获卵数,改善卵巢反应性,增加IVF妊娠率。     

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.     

Inhibin A/B in HMG or recombinant FSH ovarian stimulation with cetrorelix medication

The inhibins are valuable factors in the assessment of the quality of an ovarian stimulation cycle. In spite of good clinical results with recombinant FSH and multiple dose LHRH- antagonist (Cetrotide((R))) administration, there remains a theoretical concern that in cycles stimulated with recombinant FSH, devoid of any LH activity, not enough endogenous LH is available to guarantee good follicle maturation. A total of 287 serum samples from 41 patients was assessed: 20 patients received ovarian stimulation with recombinant FSH, 21 patients with HMG and multiple dose Cetrotide administration. Inhibin A and B were measured on cycle days 2 and 6, the day of HCG administration, the day of embryo transfer as well as 7 and 14 days after the transfer. The two patient groups were similar with regard to age, amount of gonadotrophins required and number of follicles >18 mm and 15-18 mm. Inhibin A and B concentrations were comparable throughout the stimulation, thus indicating the equality of ovarian stimulation with recombinant FSH/HMG and midcyclic antagonist administration. Higher inhibin B concentrations throughout the stimulation were correlated with a higher oocyte yield. The small number of pregnancies prevented assessment of the relationship between inhibin B values and pregnancy rate.     

LH improves early follicular recruitment in women over 38 years old

Although the capacity of recombinant FSH alone to induce folliculogenesis is undisputed, many believe that follicular recruitment in women over 38 years old could be improved by supplementing rFSH with human menopausal gonadotrophin (HMG). The present study sought to determine whether recombinant LH could reproduce the effect of HMG in women over 38 years during ovulation induction. Fifty-eight patients received rFSH (225 IU/day) supplemented with one ampoule of HMG (75 IU of FSH/75 IU of LH/HCG per day) for 5 days. Another 36 patients received rFSH (300 IU/day) supplemented with one ampoule of rLH (75 IU/day), also for 5 days. Both groups of patients received similar amounts of rFSH (1500 IU), LH/HCG (375 IU) and rLH (375 IU) and recruited a similar number of follicles as counted on day 6 (4.07 +/- 3.1 in the HMG group versus 3.7 +/- 3.2 in the LH group respectively) or on the day that human chorionic gonadotrophin (HCG) was indicated (6.5 +/- 2.7 versus 5.8 +/- 2.5 respectively). Ovarian stimulation was shorter, but not significantly so, in the group of patients receiving rFSH + HMG (10.5 +/- 1.7 days) than in the group of patients treated with rFSH +/- rLH (12 +/- 1.8 days). Significantly more MII oocytes were seen in the group treated with rFSH + rLH than in the group treated with rFSH + HMG (93.1 versus 75.3%, P < 0.05). With respect to pregnancy rates, 14/54 (26%) patients receiving rFSH + HMG and 16/34 (47%) patients receiving rFSH + rLH had a positive serum HCG. No significant difference in the number of miscarriages was observed between the two groups. In conclusion, the present results seem to indicate that rLH could be the HMG component that aids early follicular recruitment.     

Combination of recombinant follicle stimulating hormone with human menopausal gonadotrophin or recombinant luteinizing hormone in a long gonadotrophin-releasing hormone agonist protocol: a retrospective study

Purpose

To assess the effect of supplementation with recombinant human luteinizing hormone (rhLH) for patients treated either with recombinant follicle stimulating hormone (rFSH) plus rhLH or with rFSH plus human menopausal gonadotrophin (HMG) in a long gonadotrophin-releasing hormone (GnRH) agonist-stimulation protocol.

Methods

A single-centre, retrospective analysis of patients with hypo responsiveness to a long GnRH agonist protocol (n?=?174), with consecutive in-vitro fertilization or intracytoplasmic sperm injection cycles, compared the outcomes of long luteal GnRH agonist ovarian stimulation using rFSH combined with HMG (n?=?100) versus rFSH combined with rhLH (n?=?74). The endpoints included clinical pregnancy, number of oocytes retrieved, and total gonadotrophin dose.

Results

Significantly more clinical pregnancies were achieved after stimulation with rFSH and rhLH than after stimulation with rFSH and HMG (35.1 vs. 19%, p?<?0.01). More oocytes were recovered (13.1 vs. 11.3, p?=?0.024) with less FSH utilized in the rFSH and rhLH group than in the rFSH and HMG group (2706.4 vs. 4134.2?U, p?<?0.001).

Conclusions

Use of rFSH combined with rhLH in long GnRH agonist assisted reproductive technology (ART) cycles was associated with more clinical pregnancies, recovery of more oocytes, and reduction in gonadotrophin use, suggesting that the superior purity and consistency of rFSH and rhLH may result in better clinical outcomes.     

Results of controlled ovarian stimulation for ART in poor responders according to the short protocol using different gonadotrophins combinations

Introduction Improving pregnancy rates in intricate cases of ovarian stimulation remains a challenge during IVF and intracytoplasmic sperm injection (ICSI). Different protocols of ovulation induction have been proposed.Methods The short protocol of ovarian stimulation using recombinant follicle-stimulating hormone (rFSH) with or without the use of luteinizing hormone (LH) in IVF or ICSI outcome in patients with many failed attempts and maternity age 37 years was investigated. The prognostic significance of high but normal values of day 3 serum FSH concentrations was also evaluated.Results Results show that FSH levels of >9 mIU/ml are associated with poor results even with the use of human menopausal gonadotrophin (HMG). Results were generally comparable when rFSH was used alone or in combination with HMG, except for the quality and the number of embryos transferred, the later being better in the rFSH + HMG group.Conclusion In conclusion intricate cases have good chances for achieving a pregnancy using the short protocol and the outcome is further improved when LH is added from the beginning of ovarian stimulation. A slight elevation of day 3 FSH seems to be a strong prognostic factor for a poor outcome.     

A comparison between follitropin alpha filled by mass and follitropin alpha filled by bioassay in the same egg donors

This study assessed the ovarian stimulation characteristics of recombinant follitropin alpha filled by mass (rFSH-fbm) versus recombinant follitropin alpha filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose) and the second one with rFSH-fbm (Gonal-f RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin alpha filled by mass as opposed to follitropin alpha filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.     

Association between ovarian stimulation regime and protein metabolism of patients undergoing IVF/ICSI therapy

The aim of this study was to determine the relationship between the ovarian stimulation protocol (with HMG or FSH) after down-regulation with GnRH anologa and protein (total protein and albumin) as well as bilirubin and urea in serum. Furthermore, it was intended to find out the effect of these parameters on IVF/ICSI outcome. 50 patients were included in this study. All patients underwent controlled ovarian hyperstimulation for assisted reproduction therapy either with FSH (Gonal-F) or HMG (Menogon). Ovulation induction was induced by human chorionic gonadotrophine (HCG, Predalon) 10 000 IU i. m. The protein concentration (total protein, albumin) as well as bilirubin and urea concentrations were determined before down-regulation with GnRHa, at the beginning of ovarian stimulation with FSH or HMG, on the day of ovulation induction with HCG, during oocyte retrieval and fourteen days after embryo transfer. The age, body mass index and etiology of infertility showed no significant difference between patients stimulated with HMG or FSH. Total protein and albumin concentration decreased significantly (p=0.001) from 77.45 +/- 5.90 g/L and 47.02 +/- 3.41 g/L to 74.60 +/- 4.6 g/L and 45.04 +/- 2.39 g/L, respectively at the time of oocyte retrieval. Whereas, no significant change with bilirubin and urea concentration was observed. However, the mean concentration of total protein, albumin, bilirubin of patients who become pregnant was higher of those who did not. In conclusion, this study shows that total protein and albumin concentration in plasma decreased during the follicular phase significantly with the application of exogenous gonadotrophins and steroid hormones in comparison to the value before down-regulation. The mean value of total protein, albumin, bilirubin of patients who become pregnant was higher (but not significant) of those who did not. However, the high individual variation in the present results shows that these parameters are not useful as a predictor of IVF/ICSI outcome.     

A comparison between follitropin α filled by mass and follitropin a filled by bioassay in the same egg donors

This study assessed the ovarian stimulation characteristics of recombinant follitropin a filled by mass (rFSH-fbm) versus recombinant follitropin a filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose?) and the second one with rFSH-fbm (Gonal-f? RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin a filled by mass as opposed to follitropin a filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.     

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。     

The use of a long-acting gonadotropin-releasing hormone analog(D-Trp-6-LHRH) for improvement of ovarian stimulation in assisted conception programs.

To assess the efficacy of gonadotropin-releasing hormone analog (GnRHa) as an adjuvant in controlled ovarian stimulation in assisted conception programs, 114 infertile patients, who were treated by in vitro fertilization and embryo transfer (n = 61) or tubal embryo transfer (n = 53), were randomized sequentially to receive ovarian stimulation according to two protocols. In protocol 1 (n = 57), long-acting GnRHa (D-Trp-6-LHRH) microcapsules were administered intramuscularly at menstruation and ovarian stimulation using follicle-stimulating hormone (FSH) and human menopausal gonadotropin (hMG) was started 2 to 3 weeks later when the pituitary was completely suppressed. In protocol 2 (n = 57), patients received FSH and hMG from day 3 of the cycle without GnRHa pre-treatment. We found that premature luteinization did not occur in patients treated with protocol 1, and the number of cycles cancelled was also decreased. The days of ovarian stimulation and the amount of hMG required to achieve adequate follicular development were significantly higher in protocol 1 than that in protocol 2. Similarly, the mean serum estradiol levels on the day of human chorionic gonadotropin administration, number of large follicles (mean diameter greater than 10 mm), number of oocytes recovered and number of embryos obtained were also significantly higher in patients treated with protocol 1. The data suggest that the use of D-Trp-6-LHRH as an adjuvant in ovarian stimulation is associated with a lower incidence of cycle cancellation and an improvement in ovarian response in assisted conception programs.     

Luteal phase characteristics following GnRH antagonist or agonist treatment - a comparative study

Due to inherent differences between gonadotrophin-releasing hormone (GnRH) antagonists and agonists, their late effect on ovarian steroidal production during the luteal phase of IVF cycles may differ. The aim of this study was to characterize and compare the luteal phase hormonal profile after the use of GnRH antagonists or agonists in ovarian stimulation protocols for IVF, in non-conception cycles, to avoid the effect of human chorionic gonadotrophin (HCG) during the luteal phase in conception cycles. Seventy-eight normo-ovulatory patients <35 years old, undergoing IVF due to male or tubal infertility were randomly allocated either to a GnRH antagonist (study group) or GnRH agonist treatment (control group). Similar standard luteal support was given to all patients, using vaginal micronized progesterone. In non-conception cycles, no statistically significant differences were found comparing luteal phase. oestradiol or progesterone levels in the study and control groups. No statistically significant differences were found comparing the hormonal profile dynamics, the mid-luteal (HCG day +8) oestradiol/progesterone ratio and the percentage of mid-luteal oestradiol decline between the study and control groups. In conclusion, similar characteristics and dynamics of luteal phase oestradiol and progesterone were demonstrated comparing ovarian stimulation for IVF using GnRH agonist or antagonists, under similar luteal support.     

Anti-Müllerian hormone: a marker for oocyte quantity, oocyte quality and embryo quality?

Serum anti-Müllerian hormone (AMH) concentrations decline with increasing age and constitute a sensitive marker for ovarian ageing. In addition, basal serum AMH concentrations predict ovarian response during IVF cycles. Concomitantly, oocyte quantity and embryo quality decrease with advancing age. Hence, it was postulated that AMH in serum constitutes a marker for embryo quality. Women aged 37 years and younger with regular menstrual cycles, normal body mass index and partners with normal semen parameters were randomly assigned to either a standard or mild stimulation protocol for IVF treatment. Blood samples were drawn at cycle day 3 and at the day of human chorionic gonadotrophin administration. Embryo quality was assessed using embryo morphology score and preimplantation genetic screening. Serum AMH concentrations on cycle day 3 were correlated with the number of oocytes retrieved in both groups. AMH and embryo morphology were correlated after mild stimulation, but not after conventional ovarian stimulation. AMH and the chromosomal competence of embryos were not correlated. Serum AMH is predictive for ovarian response to stimulation. However, the lack of a consistent correlation with embryo morphology and embryo aneuploidy rate is not in favour of a direct relationship between oocyte quantity and embryo quality.