Precycle administration of GnRH antagonist and microdose HCG decreases clinical pregnancy rates without affecting embryo quality and blastulation

The outcome of a novel protocol utilizing precycle gonadotrophin-releasing hormone (GnRH) antagonist administration and LH activity support with microdose recombinant human chorionic gonadotrophin (HCG) was compared to GnRH agonist long protocol used in patients undergoing their first ICSI (n=707) or IVF (n=571) cycles, which had resulted in one or two blastocyst transfers. In GnRH antagonist cycles, cetrorelix acetate (3 mg) was administered s.c. 4 days before FSH stimulation and a repeat dose was given when the lead follicular diameter was 13-14 mm. LH support was provided by recombinant HCG (2.5 microg). Embryo progression and blastulation were evaluated using embryo progression indices and blastocyst quality scores. The tested protocol demonstrated reduced implantation and clinical pregnancy rates as compared with GnRH agonist long protocol, although the embryo progression and blastulation parameters and blastocyst quality were comparable among the groups. Logistic regression models further supported the significant negative impact of GnRH antagonist/microdose HCG protocol on clinical pregnancy rates in both ICSI and IVF patients. Assisted reproduction cycles with fresh blastocyst transfers utilizing precycle GnRH antagonist administration and microdose HCG support resulted in lower implantation and clinical pregnancy rates as compared with GnRH agonist cycles, although the embryo progression and blastulation parameters were comparable.     

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.     

Comparable effectiveness using flexible single-dose GnRH antagonist (cetrorelix) and single-dose long GnRH agonist (goserelin) protocol for IVF cycles--a prospective, randomized study

This prospective randomized study compared the effectiveness of a flexible single-dose gonadotrophin-releasing hormone (GnRH) antagonist (cetrorelix) and a single-dose long GnRH agonist (goserelin) protocol for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. All patients from the waiting list were successively included in the study, pre-programmed with an oral contraceptive, and randomized into goserelin and cetrorelix groups. Depending on the date on which their menstrual period started, patients took oral contraceptives for one or two cycles. Ultimately, 236 patients in the first group received a single dose of depot preparation of goserelin and 224 patients received a single 3 mg dose of cetrorelix in the late follicular phase, when the mean follicle diameter exceeded 12 mm. The mean number of ampoules of FSH and the duration of stimulation was statistically significantly lower in the cetrorelix group than in the goserelin group (25.9 versus 34.5, and 9.6 versus 12.2 days, P < 0.01). The mean number of oocytes retrieved was similar (6.7 +/- 4.5 versus 7.2 +/- 4.6, NS). Similar results were observed in fertilization rates, blastulation rates and blastocyst transfer rates in both groups. Clinical pregnancy and delivery rates per cycle were higher in the goserelin group (34.3 and 30.1%) than in the cetrorelix group (31.9 and 28.3%), but the differences were not statistically significant. The flexible single-dose GnRH antagonist protocol is an advantageous alternative to the long GnRH agonist protocol, with similar efficacy, shorter duration, a significant reduction in the number of FSH ampoules used and without the menopause-like effects of the GnRH antagonist.     

Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.     

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/1 on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.     

High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist

High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/l on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.     

Reproductive outcome using a GnRH antagonist (cetrorelix) for luteolysis and follicular synchronization in poor responder IVF/ICSI patients treated with a flexible GnRH antagonist protocol

To investigate the possible beneficial effect of a new stimulation protocol (termed 'CRASH') on the outcome of poor responder patients, a multicentre, prospective longitudinal study including a total of 36 women undergoing 72 IVF/intracytoplasmic sperm injection (ICSI) cycles with patients serving as their own controls, was conducted. A poor responder patient was defined as a patient with four or fewer oocytes extracted from five or fewer follicles and with a total FSH consumption exceeding 2000 IU in a preceding long agonist down-regulation protocol. The CRASH protocol included 3 mg of the gonadotrophin-releasing hormone (GnRH) antagonist cetrorelix given in the late luteal phase on cycle day 23. Stimulation with recombinant human FSH (rhFSH) started on cycle day 2, followed by a flexible GnRH antagonist protocol. The results showed significantly more follicles (5.4 versus 3.5), oocytes (4.3 versus 2.4) and transferable embryos (1.8 versus 0.8) with the CRASH protocol as compared with the preceding long protocol (P < 0.005 in all cases). The implantation rate and pregnancy rate per transfer was 18.4 and 38.5% respectively, approaching the clinical outcome of normal responder patients. The CRASH protocol thus may constitute an attractive alternative to conventional protocols for low responder patients, improving their clinical outcome.     

Increasing the dose of human menopausal gonadotrophins on day of GnRH antagonist administration: randomized controlled trial

A significantly lower pregnancy rate following the gonadotrophin-releasing hormone (GnRH) antagonist protocol as compared with the long GnRH agonist protocol has been reported. The objective of this study was to investigate whether increasing the dose of gonadotrophins on the day of antagonist administration would increase the pregnancy rate. This study is an open labelled, randomized controlled trial and allocation was done using sealed envelopes. One hundred and fifty-one subfertile couples undergoing IVF/intracytoplasmic sperm injection (ICSI) cycles were included in the study. Ovarian stimulation was started on day 3 of the cycle, using 150-300 IU human menopausal gonadotrophin (HMG)/day. From day 8 onward, daily vaginal ultrasound and daily urinary LH estimation were performed. If a premature LH rise was detected, the cycle was cancelled. The antagonist (0.25 mg daily) was started when the leading follicle reached 15 mm in mean diameter and LH testing in urine was negative up to and including the day of human chorionic gonadotrophin (HCG) injection. Patients were randomized on the day of starting the antagonist into two groups: group A, 72 patients with no increase in HMG dose, and group B, 79 patients in whom the dose of HMG was increased by 75 IU on the day of antagonist administration, and continued till the day of HCG administration. The results showed no statistically significant difference between the groups regarding number of oocytes retrieved, embryos obtained, implantation rate, clinical pregnancy rate and multiple pregnancy rate. It was concluded that there is no clinical evidence for increasing the dose of HMG on the day of antagonist administration.     

Randomized trial to compare the effect of recombinant human FSH (follitropin alfa) with or without recombinant human LH in women undergoing assisted reproduction treatment

Women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility were randomly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH (r-hFSH; Gonal-F) and recombinant human LH (r-hLH; Luveris) (n = 212) starting on day 6 of FSH stimulation until human chorionic gonadotrophin (HCG) at a daily fixed dose of 150 IU r-hLH, or with r-hFSH alone (n = 219). There was no significant difference in the number of metaphase II oocytes retrieved (10.3 versus 10.4) in patients treated with r-hFSH and r-hLH versus r-hFSH alone; however, more embryos were transferred in the LH-supplemented group (2.9 versus 2.8, P = 0.037). Overall, the implantation rates were 22.9 versus 27.0% in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively (NS). The respective numbers of MII oocytes retrieved in patients <35 or >or=35 years were 11 versus 8.3 (P = 0.010) for patients treated with r-hFSH alone, and 10.7 versus 9.3 (NS) for those given supplemental r-hLH (150 IU) from day 6. Implantation rates in patients <35 years treated with r-hFSH were higher (30.7%) than those receiving r-hFSH and r-hLH, (23.5%) (P = 0.068). In patients >or=35 years, the implantation rates were 21.7% for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7% when treated with FSH alone (NS). Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol, but women >or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH.     

Outlook: who needs LH in ovarian stimulation?

LH plays a key role in the intermediate-late phases of folliculogenesis. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women. Experience suggests that in about 10-12% of young normogonadotrophic patients treated with a gonadotrophin-releasing hormone agonist (GnRH-a) long protocol plus recombinant FSH human (r-hFSH), a 'steady response' is observed. In this subgroup of women, a higher number of oocytes is retrieved when daily LH activity supplementation is given from stimulation day 8, if compared with the standard FSH dose increase. Another subgroup of patients who may benefit from LH activity supplementation are those at risk for poor ovarian response treated with GnRH antagonist. Recent data demonstrate that in these women, when GnRH is administered in a flexible protocol, the concomitant addition of recombinant human LH improves the number of mature oocytes retrieved, when compared with the standard GnRH-a flare-up protocol. Thus, well calibrated LH administration improves the ovarian outcome in patients >35 years, in those showing an initial abnormal ovarian response to r-hFSH monotherapy, and in 'low prognosis' women treated with GnRH antagonists.     

Who needs LH in ovarian stimulation?

LH plays a key role in the intermediate-late phases of folliculogenesis. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women. Experience suggests that in about 10-12% of young normogonadotrophic patients treated with a gonadotrophin-releasing hormone agonist (GnRH-a) long protocol plus recombinant FSH human (r-hFSH), a 'steady response' is observed. In this subgroup of women, a higher number of oocytes is retrieved when daily LH activity supplementation is given from stimulation day 8, if compared with the standard FSH dose increase. Another subgroup of patients who may benefit from LH activity supplementation are those at risk for poor ovarian response treated with GnRH antagonist. Recent data demonstrate that in these women, when GnRH is administered in a flexible protocol, the concomitant addition of recombinant human LH improves the number of mature oocytes retrieved, when compared with the standard GnRH-a flare-up protocol. Thus, well calibrated LH administration improves the ovarian outcome in patients >35 years, in those showing an initial abnormal ovarian response to r-hFSH monotherapy, and in 'low prognosis' women treated with GnRH antagonists.     

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.     

Ovarian hyperstimulation induced by a GnRH agonist. About one case

We report a case of ovarian hyperstimulation induced by a GnRH agonist (Decapeptyl in a patient aged of 23 years and having 3 years of primary infertility of male origin. Twelve days after agonist administration, several ovarian follicles, great-sized, and with a rate of elevated serum oestradiol have been noted. After triggering of the ovulation by 5000 IU of HCG, oocyte retrieval permitted the collection of 4 oocytes 3 of which were mature. Only one embryo with 4 cells has been transferred 48 hours after intracytoplasmic sperm injection fertilization (ICSI), but there was no pregnancy. Ovarian hyperstimulation induced by GnRH agonist is a rare event and only a few cases have been reported. The development of multiple follicles after the administration of an agonist is a paradoxal answer of the ovary to the pituitary desensitization without a clarified physiopathology. The hypothesis of a direct action of the agonist on the ovary is likeliest. Triggering of ovulation by human chorionic gonadotrophin (HCG) has been achieved by certain authors. Fertilization of oocytes and transfers of embryos have succeeded in certain cases, but only one pregnancy has been reported that led to a living birth.     

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.     

Effectiveness of a low gonadotrophin-releasing hormone antagonist dose in preventing premature luteinizing hormone rise during controlled ovarian stimulation

The current prospective randomized study was designed to test the efficacy of a low dose (0.125 mg/day) of the gonadotrophin-releasing hormone antagonist cetrorelix in preventing premature luteinizing hormone (LH) rise during controlled ovarian stimulation in comparison with the standard dose of 0.25 mg/day. Ovarian stimulation was started with 225 IU of recombinant follicle stimulating hormone (FSH) on day 2 of the menstrual cycle. Cetrorelix was injected daily from day 6 of gonadotropin administration. Blood was sampled from each woman on day 3 of ovarian stimulation and then daily from day 5 onward up to human chorionic gonadotropin administration for analysis of FSH, LH, progesterone, and estradiol. LH rise was defined as serum LH?≥10 mIU/ml. There were 40 patients receiving cetrorelix at 0.25 mg/day and 36 patients receiving cetrorelix at 0.125 mg/day. Premature LH rise was recorded in 10% of patients injecting antagonist at 0.25 mg/day and in 14% of patients administered with antagonist at 0.125 mg/day. These frequencies did not differ statistically. In conclusion, our results suggest that a cetrorelix dose of 0.125 mg/day is effective as the standard dose (0.25 mg/day) in preventing premature LH rise during controlled ovarian stimulation.     

Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre,multinational, phase IIIb clinical experiences

Gonadotrophin-releasing hormone antagonists are effective and safe in preventing premature LH surges, a leading cause of cycle cancellation or failure during assisted conception. Two studies assessed two administration regimens for cetrorelix (as Cetrotide): the multiple-dose (MD, 0.25 mg/day, n = 1066) and single-dose (SD, 3 mg, n = 541) protocols. Patient outcomes were very similar: >90% reached criteria for human chorionic gonadotrophin (HCG) administration and underwent oocyte retrieval; embryo transfer was performed in 83-84%; failure to retrieve oocytes was rare (0.8%); on average, 11 follicles > or =10 mm in diameter were seen on the day of HCG administration. The SD protocol was associated with higher numbers of oocytes retrieved and available for insemination, although the numbers of embryos obtained or transferred were comparable. A total of 251 and 121 pregnancies were reported in the MD and SD groups respectively. Pregnancy rates per embryo transfer were 27 and 28% respectively. Severe ovarian hyperstimulation syndrome (OHSS) occurred in <1% of cycles. Twelve per cent of patients reported local reactions to injections in the MD group, compared with 8% in the SD group; none was serious or led to discontinuation. Seventy-three per cent of patients in the SD group received only one injection. These two studies therefore show that the single-dose cetrorelix protocol offers equal efficacy and safety to the MD regimen, while having the advantage of requiring only one injection in most patients.     

Impact of high basal FSH/LH ratio in women with normal FSH levels on in vitro fertilization outcomes

Abstract

Basal luteinizing hormone (LH) levels have also been suggested to impact on ovarian responsiveness as well as basal follicular stimulating hormone (FSH) levels. The aim of this study was to compare the in vitro fertilization (IVF) outcomes according to cycle day 3 FSH/LH ratio and to assess the proper stimulation protocol between gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols. The retrospective cohort study recruited a total of 1211 women having the laboratory values of FSH (<10?IU/L) and LH within 3 months before IVF. Patients were treated with GnRH agonist long or GnRH antagonist protocols and stimulated with recombinant FSH (rFSH). The number of total retrieved oocytes and mature oocytes, implantation rate, clinical pregnancy rate and ongoing pregnancy rate were analyzed between groups: Group I: FSH/LH?<?2 and Group II: FSH/LH?≥?2. The Group II had the small number of retrieved oocytes and mature oocytes compared to the Group I (p?=?0.000). Clinical and ongoing pregnancy rate were lower in Group II (p?=?0.006, 0.006, respectively). In comparison of each protocol within groups, Group II showed significantly low pregnancy rate when GnRH antagonist was administered. In women with normal FSH level, high day 3 FSH/LH ratio can present subclinically low ovarian reserve and be predictive of lower pregnancy outcomes in fresh IVF cycles, and the choice of GnRH agonist can be related to favorable IVF outcomes.     

Low-dose GnRH antagonist protocol is as effective as the long GnRH agonist protocol in unselected patients undergoing in vitro fertilization and embryo transfer

ObjectiveThe present retrospective and controlled comparative study was designed to evaluate the pregnancy rate achieved using a modified, fixed, multiple-dose 0.125 mg gonadotropin-releasing hormone (GnRH) antagonist protocol with the long GnRH agonist protocol as the control group.Materials and methodsOne hundred and twenty unselected women between 30 and 40 years of age, in their first cycle of IVF/ICSI, with a baseline follicle-stimulating hormone (FSH) <10 IU and an antral follicle count >3 were assigned into two groups: (1) the study group received 0.125 mg of cetrorelix daily starting on Day 6 of stimulation; and (2) the control group received leuprolide daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a flexible dose of recombinant FSH for stimulation. An ongoing pregnancy rate of more than 12 weeks was the primary outcome measure of the study.ResultsPrimary and secondary outcomes were comparable in both groups. A shorter duration of stimulation, a lower dosage of recombinant FSH consumption and a thinner endometrium on the day of human chorionic gonadotropin administration were all observed in the GnRH antagonist group.ConclusionA dosage of 0.125 mg GnRH antagonist protocol was effective for these unselected patients during IVF/ET.     

Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study

OBJECTIVE: To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART). STUDY DESIGN: A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed. RESULTS: None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively). CONCLUSION: The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.     

Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer

Background.?The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome.

Methods.?A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12–14 mm. GnRH agonist was administered in a long luteal protocol.

Results.?The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups.

Conclusions.?Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.