Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 μg corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ≥11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (Cl) 0.5-1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% Cl 1.4-2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar.     

Pharmacokinetics and follicular dynamics of corifollitropin alfa versus recombinant FSH during ovarian stimulation for IVF

A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. This double-blind randomized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150 μg corifollitropin alfa versus daily 200 IU rFSH in 1509 patients. Comparative analyses were performed on serum concentrations of FSH immunoreactivity (pharmacokinetics), and the number and size of growing follicles, and inhibin B and oestradiol concentrations as biomarkers of ovarian response (pharmacodynamics). The rate of follicular development was similar in both treatment groups. By stimulation day 8, 33% of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin (HCG) injection. The number of follicles ?11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 (difference, 1.2; 95% confidence interval (CI) 0.5–1.8; P < 0.01) and on the day of HCG injection (difference, 2.1; 95% CI 1.4–2.8; P < 0.01). The rise of inhibin B and oestradiol concentrations was similar in both treatment groups. Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar.A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH (rFSH) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection. The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH. A total of 1509 patients were randomized in a double-blind, controlled trial to either a single injection of 150 μg corifollitropin alfa or to daily injections of 200 IU rFSH for the first 7 days of ovarian stimulation. Serum levels of FSH immunoreactivity were analysed (pharmacokinetic analysis), together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response (pharmacodynamic analysis). Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards, when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached. Corifollitropin alfa treatment resulted in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH. It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar.     

No association between endogenous LH and pregnancy in a GnRH antagonist protocol: part II, recombinant FSH

The association between endogenous LH concentrations during ovarian stimulation in a gonadotrophin-releasing hormone (GnRH) antagonist protocol and pregnancy likelihood was examined in a large combined analysis of individualized patient data obtained after treatment with recombinant FSH and a GnRH antagonist prior to IVF/intracytoplasmic sperm injection. Data from 1764 patients from six randomized controlled trials were pooled for retrospective analysis. Ongoing pregnancy and miscarriage rates for patients stratified by LH percentiles were assessed. Patients in the lowest LH quartile (< P25) were younger with a higher predicted ovarian reserve and response compared with patients in the highest quartile (> P75). With adjustment for identified predictive factors of pregnancy, estimated odds ratios (95% confidence interval) for ongoing pregnancy for LH categories < P25 versus ≥ P25, > P75 versus ≤ P75 and < P25 versus > P75 were 0.96 (0.75-1.22), 1.13 (0.88-1.45) and 0.89 (0.66-1.21) on stimulation day 8, and 0.96 (0.76-1.21), 1.03 (0.82-1.30) and 0.95 (0.72-1.26) on the day of human chorionic gonadotrophin, respectively. No significant differences in pregnancy or miscarriage rates between the LH categories were observed. Endogenous LH concentrations have no association with the likelihood of ongoing pregnancy in women undergoing ovarian stimulation using a recombinant FSH/GnRH antagonist protocol.     

Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women

In this double-blind, double-dummy, randomized, equivalence trial (Ensure), 396 women weighing 60 kg or less who underwent controlled ovarian stimulation prior to IVF or intracytoplasmic sperm injection were randomized in a 2:1 ratio to a single dose of 100 μg corifollitropin alfa or daily 150 IU recombinant FSH (rFSH) for the first 7 days of stimulation in a gonadotrophin-releasing hormone antagonist protocol. The mean ± SD number of oocytes retrieved per started cycle was 13.3 ± 7.3 for corifollitropin alfa versus 10.6 ± 5.9 for rFSH. The estimated treatment difference of +2.5 oocytes (95% CI 1.2–3.9) in favour of corifollitropin alfa (P < 0.001) was well within the predefined equivalence margin. The median (range) duration of stimulation was 9 (6–15) days in both groups. In 32.8% of the patients, one injection of corifollitropin alfa was sufficient to reach the human chorionic gonadotrophin criterion. The incidence of moderate and severe ovarian hyperstimulation syndrome was 3.4% for corifollitropin alfa and 1.6% for rFSH. A dose of 100 μg corifollitropin alfa offers a simplified treatment option for potential normal responder patients with a lower body weight.     

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.     

Ovarielle Stimulation mit Corifollitropin alfa

Corifollitropin alfa is a new hybrid protein of human follicle-stimulating hormone (FSH) and the C-terminal peptide of the ??-subunit of human chorionic gonadotropin. Due to a slower absorption and a longer terminal half-life, corifollitropin alfa can induce multifollicular development in women undergoing controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist-assisted in vitro fertilization (IVF). In two large randomized, double-blind, phase III trials, a single subcutaneous injection of corifollitropin alfa was as effective as 7 daily injections of recombinant FSH in inducing multifollicular development when used as part of a GnRH antagonist protocol. Non-inferiority in ongoing pregnancy rates and numbers of oocytes available for IVF has been established. In another large phase III trial, non-immunogenicity of corifollitropin alfa has been demonstrated.     

Effect of urinary versus recombinant FSH on clinical outcomes after frozen–thawed embryo transfers: a systematic review

Recent randomized trials, systematic reviews and cost-effectiveness analyses have demonstrated the relative efficacy, and in some cases superiority, of urinary gonadotrophins (uFSH, human menopausal gonadotrophin) compared with recombinant FSH (rFSH). However, the effectiveness of frozen-embryo transfers (FET) following ovarian stimulation with uFSH versus rFSH in the fresh cycle has not been well investigated. The objective of this study was to determine whether there are differences in clinical outcomes in women undergoing FET according to the type of gonadotrophin used during ovarian stimulation. Following a meticulous search, all published comparative studies of FET using ovarian stimulation were reviewed. Data on clinical outcomes were extracted and systematically presented. Using the agonist long protocol for down-regulation, five trials provided extractable data for live-birth and ongoing pregnancy rates following FET, as well as the cumulative live-birth, ongoing pregnancy and clinical pregnancy rates following fresh-embryo transfer and FET from the same cycle. There was no evidence of significant effect difference between the uses of uFSH versus rFSH regarding any of the outcomes. In conclusion there is insufficient evidence to determine whether the use of a certain type of gonadotrophin during ovarian stimulation affects the clinical outcomes in subsequent FET.Clinical efficiency in IVF procedures has been debated for years. Defining a unified goal, or endpoint, for IVF treatments has shown marked discrepancies among clinicians, regulatory bodies and organizations; with some regarding a clinical pregnancy, an ongoing pregnancy, a live-birth, or even a take-home baby as the primary outcome of IVF treatments. The objective of this systematic review was to determine the effectiveness of the use of urinary versus recombinant FSH on the results of frozen embryo transfers and the effect that this would have on the cumulative clinical results of IVF. This systematic review has shown that there is insufficient evidence to determine whether the use of a certain type of gonadotrophin during ovarian stimulation affects the clinical outcomes in subsequent frozen embryo transfers, such as live-birth rate, ongoing pregnancy rate, clinical pregnancy rate. With respect to cumulative rates, it is noted that no significant differences in live birth rate, ongoing pregnancy rate, and clinical pregnancy rate following fresh and frozen transfer cycles. It is concluded that well-designed and powered studies are needed to determine possible effects of the use of a certain type of gonadotrophin during ovarian stimulation on the clinical outcomes in subsequent frozen thawed embryo transfers.     

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.     

Recombinant LH supplementation to recombinant FSH during induced ovarian stimulation in the GnRH-antagonist protocol: a meta-analysis

This study aims to compare the efficacy of recombinant LH (rLH) supplementation for ovarian stimulation in gonadotrophin-releasing hormone-antagonist protocol for IVF/intracytoplasmic sperm injection cycles. Search strategies included online surveys of databases. The fixed effects model was used for odds ratio (OR) and effect size (weighted mean difference, WMD). Five trials fulfilled the inclusion criteria. When the meta-analysis was carried out, advantages were observed for the LH supplementation protocol with respect to higher serum oestradiol concentrations on the day of human chorionic gonadotrophin administration P < 0.0001; WMD: 514, 95% CI 368, 660) and higher number of mature oocytes (P = 0.0098; WMD: 0.88, 95% CI 0.21, 1.54). However, these differences were not observed in the total amount of recombinant FSH (rFSH) administered, days of stimulation, number of oocyets retrieved, the clinical pregnancy rate per oocyte retrieval, the implantation rate and miscarriage rate. This result demonstrates that the association of rLH with rFSH may prevent any decrease in oestradiol after antagonist administration and that a significantly higher number of mature oocytes was available for laboratory work. Nevertheless, it failed to show any statistically significant difference in clinically significant end-points in IVF (implantation and pregnancy rates). Additional randomized controlled trials are needed to confirm these results further.     

体外受精超促排卵治疗中单用促性腺激素和拮抗剂方案临床结局的比较

目的探讨体外受精(IVF)治疗中单用促性腺激素(Gn)对妊娠结局的影响。方法月经第3日开始给予重组卵泡刺激素(rFSH)促排卵,促排卵第6日开始监测血激素水平和阴道超声监测卵泡大小。将达到思则凯添加标准者[黄体生成素(LH)5 IU/L,或LH/基础LH≥3]设为对照组,每日给予思则凯0.125 mg直至人绒毛膜促性腺激素(hCG)注射日;以未达到标准不使用思则凯者设为研究组。结果研究组(n=31)和对照组(n=49)患者在Gn剂量、促排卵天数、hCG注射日血清内分泌水平、获卵数、受精率、着床率、临床妊娠率和活产率方面均无统计学差异(P0.05)。结论在IVF促排卵治疗中,通过对血清LH的监测,如果LH维持在低水平可以不给予拮抗剂治疗,单纯使用Gn是一种经济有效的促排卵方案。     

Replacing HMG/FSH by low-dose HCG to complete corifollitropin alfa stimulation reduces cost per clinical pregnancy: a randomized pragmatic trial

Research questionThe cost of IVF treatment remains high, among other factors because of the medication needed for ovarian stimulation. This study investigated the effect of using low-dose human chorionic gonadotrophin (HCG) for the second phase of follicular maturation after corifollitropin alfa induction, to replace the more expensive, either recombinant or human menopausal gonadotrophin (HMG), on the cost of ovarian stimulation.DesignOne hundred and five patients were randomly divided into two groups: patients in the HCG group (n = 50) received low-dose HCG from Day 7 until the diameter of at least three follicles reached 17 mm or more, while patients in the FSH group (n = 55) received conventional ovarian stimulation with highly purified HMG injections.ResultsThe clinical pregnancy rate in the HCG group was 38% higher than in the FSH group (number needed to treat, NNT = 13). The cost per pregnancy needed for ovarian stimulation was reduced from €4902 in the FSH group to €2684 in the HCG group. Hence, the cost of ovarian stimulation medication to obtain 10 pregnancies using the conventional FSH protocol is sufficient to attain 18 pregnancies when applying the low-dose HCG protocol.ConclusionThis study provides evidence that using HCG instead of HMG/FSH for ovarian stimulation results in a significant reduction in the cost of IVF with, at least, an equivalent pregnancy rate.     

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.     

The effect of the day of initiation of ovarian stimulation in the day of luteinizing hormone surge and outcome of in vitro fertilization

It was hypothesized that the day of initiation of ovarian stimulation may influence the day of the luteinizing hormone (LH) surge onset and follicular development. Two groups of 52 patients were randomly selected to commence ovarian stimulation on either day 2 or day 4. The mean +/- standard deviation day of the LH surge was 11.0 +/- 0.9 for day 2 and 12.2 +/- 0.9 for day 4 (P less than 0.001), and the day of human chorionic gonadotropin (hCG) administration was 10.7 +/- 1.2 for day 2 and 11.4 +/- 0.9 for day 4 (P less than 0.02). The two groups also differed significantly in the mean number of days of human menopausal gonadotropin (hMG) administration (day 2, 7.4 +/- 2.7, versus day 4, 6.3 +/- 2.5), and the mean number of vials of hMG administered (day 2, 10.4 +/- 3.2, versus day 4, 8.1 +/- 2.9). However, the mean estradiol level on the day of the LH surge or hCG administration, the number of oocytes collected and fertilized, the number of embryos transferred, and the pregnancy rates were not significantly different. In conclusion, the day of the LH surge or hCG administration can be influenced by the day of initiation of ovarian stimulation, and the initiation of ovarian stimulation around day 4 of the menstrual cycle is clinically more efficient than initiation of follicular development early in the follicular phase.     

Is corifollitropin alfa effective in controlled ovarian stimulation among all poor ovarian responders? A retrospective comparative study

Abstract

Several studies have compared the effectiveness of corifollitropin alfa versus daily gonadotropins in poor ovarian responders (PORs) undergoing controlled ovarian stimulation (COS), showing conflicting results in terms of IVF outcomes. Given the heterogeneity of patients included in the classification of POR according to ‘Bologna criteria’, the aim of this study was to evaluate the impact of corifollitropin alfa in two different categories of POR distinguished according to patients’ antral follicle count (AFC). We retrospectively evaluated 104 infertile POR, split into two groups according to AFC (Group A?≤?5; Group B?>?5) and subgroups according to the ovarian stimulation regimen (corifollitropin alfa plus daily gonadotropins (Subgroup 1) versus daily gonadotropins alone (Subgroup 2)). Outcome measures were total oocytes, MII oocytes, total embryos, follicular output rate (FORT), implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). Subgroup A1 experienced a lower number of total oocytes, MII oocytes, total embryos, and FORT (p?<?.05) in comparison to Subgroup A2, while no difference was found when comparing Subgroups B1 and B2. No difference was found between subgroups even in terms of IR, CPR, MR, and LBR. In conclusion, corifollitropin alfa may be as effective as daily gonadotropins in POR with AFC?>?5 undergoing COS, while it might be inferior to daily gonadotropins in POR with AFC?≤?5.     

人绒毛膜促性腺激素在卵泡发育中的作用

目的:过去多年,由于人绒毛膜促性腺激素(hCG)与黄体生成素(LH)高度相似,hCG已代替LH被应用于促进卵子的最后成熟。最近,人们发现LH/hCG受体遍布所有的生殖器官,提示hCG的作用不限于此。与LH相比,hCG的半衰期更长、与LH/hCG受体结合更为紧密,效应可能更强。已经有研究报道低剂量hCG可独立于卵泡刺激素(FSH)支持中晚期卵泡的发育与成熟。在控制性超促排卵(COH)之前以及早期添加hCG可能是个有效的减少重组FSH的用量,提高卵子质量,提高妊娠率的方法。本文主要从LH在激素合成以及卵泡发育中的作用,hCG与LH的异同,hCG在中晚期卵泡和早期卵泡发育中的作用等方面进行介绍hCG的最新应用进展。     

Recombinant FSH vs. urinary FSH for ovarian stimulation in in vitro fertilization

OBJECTIVE: To compare ovarian stimulation with recombinant FSH (rFSH) vs. urinary FSH (uFSH) in terms of hormonal events within ovarian follicles and the outcome of in vitro fertilization. STUDY DESIGN: A prospective randomized comparative study of rFSH (n = 70) vs. uFSH (n = 61) ovarian stimulation. Hormone determinations were serum estradiol (E2) on the day of human chorionic gonadotropin (hCG) administration, and E2, androstenedione (A) and testosterone (T) at the time of follicular aspiration in the follicular fluid and serum. RESULTS: The total dose of gonadotropins required and the length of ovarian stimulation were the same in the 2 groups. In follicular fluid the E2 and the A levels were significantly higher in the rFSH group (3,065 +/- 1,646 vs. 2,368 +/- 1,240 nmol/L, P = .004, and 103.7 +/- 51.6 vs. 89.0 +/- 42.3 nmol/L, P = .042, respectively), whereas A:E2 and T:E2 ratios were significantly lower (39.6 +/- 22.5 vs. 52.3 +/- 59.6, P = .042, and 9.1 +/- 4.7 vs. 17.6 +/- 26.9, P = .006, respectively). Serum hormonal levels, number of oocytes retrieved and pregnancy rates did not differ significantly between the groups. CONCLUSION: rFSH provides results similar to those of uFSH. rFSH enhances steroidogenesis and provokes different androgen/estrogen ratios than does uFSH without influencing the outcome of in vitro fertilization.     

Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial

This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52–0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46–0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day     

Spontaneous LH surges prior to HCG administration in unstimulated-cycle frozen-thawed embryo transfer do not influence pregnancy rates

LH surges are the start of a period of optimal endometrial receptivity. Missing these surges in an unstimulated-cycle frozen-thawed embryo transfer (FET) based on ultrasound alone might lead to incorrect timing of embryo transfer. This prospective, non-randomized trial established the incidence and effect of spontaneous LH surges on ongoing pregnancy rates and assessed the use of ultrasound without LH monitoring in planning FET. All patients undergoing unstimulated-cycle FET in the study centre over a 2-year period were included in this analysis (n=233). All patients had regular menstrual cycles. Serum LH analysis took place before human chorionic gonadotrophin administration. The main outcome measure was ongoing pregnancy. LH surges occurred in over half of patients. Overall pregnancy rate was 34.3%. Relative risks for ongoing pregnancy for cycles with or without a spontaneous LH surge were not significantly different (ongoing pregnancy rate 33.4% versus 34.8%; RR 1.02, 95% CI 0.7-1.5). Based on these results, it was concluded that LH surges ≥10 IU/l occurred in over 50% of patients, but LH surges demonstrated no significant effect on pregnancy rates. Single LH determination prior to ovulation induction in unstimulated-cycle FET does not seem to have added clinical value.     

Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study

This prospective randomized pilot study was aimed at investigating the effect of the novel addition of aromatase inhibitors to an ovarian stimulation protocol for IVF or intracytoplasmic sperm injection, on endocrine parameters including serum androgen, oestrogen, progesterone, LH and FSH concentrations. The patients were randomized to receiving letrozole (group A; n = 10), versus no letrozole (group B; n = 10) in an ovarian stimulation protocol with recombinant FSH 150 IU/day starting on day 2 of the cycle, and gonadotrophin-releasing hormone antagonist 0.25 mg/day starting on day 6 of the cycle. Median LH concentrations were significantly higher (P < 0.01) in group A versus group B during letrozole administration. Median serum oestradiol concentrations were lower in group A versus group B, and median serum FSH, testosterone and androstenedione concentrations were higher in group A versus group B, throughout the follicular phase, without reaching significance. Median endometrial thickness was significantly higher (P < 0.05) in group A versus group B on the day of human chorionic gonadotrophin administration. Pregnancies were achieved. This pilot study supports the idea that aromatase inhibitors can contribute to normal potential of implantation and follicular response, without having negative anti-oestrogenic effects.     

Age-matched comparison of recombinant and urinary HCG for final follicular maturation

This age-matched retrospective analysis compared the clinical outcomes of recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down-regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in combination with human menopausal gonadotrophin. When two or more follicles had attained a mean diameter of 20 mm, follicular triggering was achieved with either Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were considered subjects, and they were age-matched in a 1:2 ratio to patients receiving uHCG, who were designated as controls. The main outcome measures were number of oocytes retrieved, number of mature oocytes obtained, number of oocytes fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched and compared with 546 controls. Recombinant HCG had a minimal effect on the number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3) and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0 versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular maturation in IVF cycles.