cetrorelix and Ovarian-Hyperstimulation-Syndrome

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in "in Vitro" Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Topics: Age Factors; Embryo Transfer; Female; Fertilization in Vitro; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Meta-Analysis as Topic; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic

This article is a systematic review of the literature on utilization of gonadotrophin-releasing hormone antagonists (GnRH-ant) for ovarian stimulation for IVF in special patient groups. Summarized by meta-analysis are the data from randomized controlled trials (RCT) in which GnRH-agonist (GnRH-a) and GnRH-ant were compared (eight RCT for poor response, four RCT for PCOS). Also reviewed are the data from two RCT and 13 retrospective or observational trials in which patients at risk of ovarian hyperstimulation syndrome (OHSS) were triggered with GnRH-agonist instead of HCG. For poor responders, no differences in clinical outcomes were found, except a significantly higher number of cumulus-oocyte complexes in GnRH-antagonist multiple dose protocol as compared to GnRH-agonist long protocol (P=0.05). For PCOS patients, no differences in outcomes were found, except a significantly shorter duration of stimulation, when GnRH-antagonist multiple dose protocol and GnRH-agonist long protocol are compared (P<0.01). However, sample sizes are still small and power to detect subtle differences is therefore limited. For OHSS risk patients triggered with GnRH-agonist, reports on the efficacy of this measure vary in the literature. GnRH-agonist triggering appears to be associated with a reduction in the incidence of mild and moderate OHSS. For prevention of severe OHSS, as yet, only very limited evidence is available.

Topics: Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Odds Ratio; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

Gonadotrophin-releasing hormone (GnRH) antagonists have been introduced in IVF to prevent premature LH surge. They bind competitively to pituitary receptors and prevent endogenous GnRH from exerting any stimulus on pituitary cells, avoiding the initial 'flare-up' effect and decreasing gonadotrophin secretion within a few hours. Pituitary reserve and gonadotrophin synthesis are not affected; therefore, the recovery of pituitary function is rapid. Two different regimes have been described. The multiple-dose protocol involves the administration of 0.25 mg cetrorelix (or ganirelix) daily from day 6-7 of stimulation, or when the leading follicle is 14-15 mm, until human chorionic gonadotrophin (HCG) administration. The single-dose protocol involves the single administration of 3 mg cetrorelix on day 7-8 of stimulation. Both antagonists with either regimen seem to be equally effective in the prevention of the LH surge. Compared with a long luteal agonist protocol, the treatment is shorter and requires a smaller amount of gonadotrophins. Pregnancy rate seems to be lower, but a decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) is reported by several studies. A promising aspect of antagonists may be the possibility of making treatment less aggressive. Finally, in antagonist cycles, ovulation triggering is possible by GnRH agonists, avoiding the deleterious effect of HCG and thus preventing OHSS.

Topics: Chorionic Gonadotropin; Clinical Protocols; Clinical Trials as Topic; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pituitary Gland

Gonadotrophin-releasing hormone (GnRH) antagonists have recently been introduced into clinical practice. They appear to offer a promising alternative to the long-established GnRH agonist regimens for prevention of a premature LH surge during ovarian stimulation for assisted reproductive techniques. Clinical outcomes achieved with antagonists are comparable with those of a long GnRH agonist protocol, while treatment times and gonadotrophin requirements are reduced and safety is improved. In particular, the antagonists appear to be associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) than do agonists. Patient surveys suggest a preference for antagonist over agonist treatment cycles. These benefits suggest that GnRH antagonists have the potential to replace agonists as the treatment of choice in ovarian stimulation for assisted reproductive techniques. Two agents, cetrorelix and ganirelix, are currently in clinical use. Cetrorelix is available in single- and multiple-dose formulations, offering increased flexibility compared with ganirelix.

Topics: Amino Acid Sequence; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Molecular Sequence Data; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins

The safety of ovarian stimulation procedures or the procedure of assisted reproduction in general can be estimated by various parameters. Two of the most important are the health of children born after the procedure and the incidence of ovarian hyperstimulation syndrome (OHSS). The latter is important because it is the most severe, potentially life-threatening complication of any stimulation procedure. The use of gonadotrophin-releasing hormone (GnRH) antagonists in ovarian stimulation protocols has had no impact on the health of children born. This was proven in 227 children born after the use of cetrorelix and in 73 children born after the use of ganirelix. To analyse the incidence of OHSS and the impact of GnRH antagonists on clinical pregnancy rates compared with the long protocol, a meta-analysis was done. This showed a reduction of OHSS with the use of cetrorelix. Furthermore, when compared with the long protocol, clinical and ongoing pregnancy rates were not significantly reduced with the use of cetrorelix. Taken together, the use of GnRH antagonists are safe with regard to children's health. The incidence of OHSS does not increase with ganirelix, and a reduction can be expected with cetrorelix.

Topics: Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infant, Newborn; Infant, Newborn, Diseases; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

Topics: Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

The introduction of the gonadotrophin-releasing hormone(GnRH) antagonists offers new potential for in vitro fertilization (IVF) clinics. Compared with GnRH agonists, the use of the GnRH antagonists significantly reduces the dose of gonadotrophin and duration of treatment required, and also reduces unwanted side-effects. Patients also tend to prefer treatment with GnRH antagonists compared with agonists. The GnRH antagonists are useful in both good and poor responders, and there is some flexibility in treatment protocols. A single dose of GnRH antagonist may be used in patients who do not want or require more aggressive stimulation. Promising data indicate advantages of GnRH antagonists in terms of reduced incidence of ovarian hyperstimulation syndrome and reduced impairment of luteal function. It is anticipated that, as a result of further development of treatment protocols, pregnancy rates with the GnRH antagonists will become at least equivalent to those achieved with GnRH agonist protocols.

Topics: Clinical Trials, Phase III as Topic; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction

The use of GnRH antagonists has revolutionized ovarian stimulation for assisted reproduction. Two GnRH antagonists are clinically available, namely, cetrorelix and ganirelix. Several studies have directly compared these new stimulation protocols against the long GnRH agonist protocol. To evaluate whether there is a reduction in cases of ovarian hyperstimulation syndrome (OHSS) and/or a reduction in pregnancy rates, a meta-analysis was performed. There was a significant reduction of OHSS cases in the cetrorelix studies (odds ratio, OR, 0.23; 95% confidence interval, CI, 0.10-0.54), but no reduction for ganirelix (OR 1.13; 95% CI 0.24-5.31). The incidence of OHSS degree III cases was reduced in the cetrorelix protocols as compared to the long protocol to a nearly significant degree (OR 0.26; 95% CI 0.07-1.01). Ganirelix did not reduce the incidence of OHSS degree III at all (OR 1.08; 95% CI 0.27-4.38). The pregnancy rate per cycle was significantly lower in the ganirelix protocols than in the long protocol (OR 0.76; 95% CI 0.59-0.98). The studies using cetrorelix showed quite similar, not significantly different results for the antagonist and the long protocol groups for the pregnancy rate per cycle (OR 0.91; 95% Cl 0.68-1.22). From the data one can conclude that cetrorelix but not ganirelix will reduce the incidence of cases of OHSS and that cetrorelix but not ganirelix will result in the same pregnancy rates as the long protocol. Several possibilities to explain this phenomenon are discussed.

Topics: Chorionic Gonadotropin; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Odds Ratio; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Reproductive Techniques, Assisted

New GnRH antagonists are available in clinical practice. The different studies have confirmed the efficacy of these antagonists in preventing the LH surge. Two protocols have been described: in the multiple dose regimens, small doses of antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG. In the single dose protocol, one injection of a larger dose (3 mg) is proposed in the late follicular phase. Local and general tolerance of the two compounds is very good. The results obtained with both regimens as compared with GnRH agonists in long protocols are showing a reduction in the stimulation length, in the consumption of gonadotrophins and in the incidence of the OHSS. The pregnancy rates are comparable in the good prognosis patients selected in the published studies. When the final tuning of these new protocols will be done, the advantages of GnRH antagonists in reducing the complications and side effects of ovarian stimulation will give to GnRH antagonists an important place in IVF.

Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ± 2730 and the mean number of retrieved oocytes was 19.7 ± 7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Risk Factors; Sperm Injections, Intracytoplasmic; Young Adult

Ovarian hyperstimulation syndrome (OHSS) is an important condition with considerable morbidity and a small risk of mortality and most commonly results as an iatrogenic condition following follicular stimulation of the ovaries. We aimed to evaluate safety and efficacy of 3-day cetrotide therapy started on day of oocyte retrieval (Day-0) in women at high-risk for development of ovarian hyperstimulation syndrome (OHSS) after GnRH agonist induction protocol.. Forty-eight women fulfilling inclusion criteria underwent ultrasound scanning for maximal ovarian diameter (MOD) estimation and ascites grading. Patients underwent embryo freezing, but the study group received 3-day Cetrotide sc injection (0.25 mg/day) started on Day-0. Serum E2, pain scores and MOD were checked daily. Hematocrite value (Ht%), total leucocytic count (TLC), gastrointestinal (GI) manifestations and ascites grading were re-evaluated on Day-3, 6 and 8.. Sequential serum E2 levels decreased significantly in both groups with significantly lower levels in the study group. Sequential MOD estimates showed non-significant difference between the two groups and versus Day-0 estimates. On Day-2, pain scores showed progressive significant decrease compared to Day-0 scores in both groups with significantly lower scores in the study group. On Day-3; four control patients still had vomiting and by Day-6, 6 of the control patients still had GI manifestations with significant difference versus the study group. Compared to Day-0 estimates, Ht% and TLC were significantly lower on Day-3, 6 and 8 in the study group, but only on Day-8 in the control group. Day-3 and Day-8 ascites grading in both groups was significantly lower compared to respective Day-0 grading with significant difference in favor of the study group. Six patients required hospitalization, but without mortalities. Day-3 E2 levels in the study group showed positive significant correlation with clinical and other laboratory data and ascites grading, while the correlation was non-significant with MOD.. The 3-day cetrotide therapy starting after oocyte retrieval with embryo transfer freezing could be an appropriate management policy for women received GnHR-agonist induction protocol and were at high-risk for OHSS. Sequential E2 serum levels could predict outcome more perfectly than sequential MOD estimates.. Trial registration ( clinicaltrial.gov registration) NCT02823080 (retrospective) Initial Release 21-6-2016 Last Release 3-1-2017 Unique Protocol ID: Benha U Secondary IDs: kmsalama.

Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Middle Aged; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Retrospective Studies

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle?. A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle.. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle.. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05.. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo.. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01).. This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use.. This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle.. None.. EudraCT number 2009-010952-81.. 21 September 2009.. 30 October 2009.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Treatment Outcome

Recently, an increased scientific interest was focused on mild approaches for ovarian stimulation in clinical practice. Milder stimulation aims to develop safer and more patient-friendly protocols which are more physiological, less drug use, less expensive and the risks of treatment are highly minimized.. To investigate the efficacy and safety of a mild ovarian stimulation protocol in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS), compared to conventional long down-regulation protocol.. This a prospective, open, randomized study, included 349 infertile patients considered at high risk of developing OHSS, undergoing in vitro fertilization treatment in two private assisted reproduction centers. The patients were randomized into two groups: group A (n = 148) had a mild/minimal stimulation protocol of recombinant FSH (rFSH) combined with GnRH antagonist. Group B (n = 201) (control group) had a standard long protocol of rFSH combined with GnRH agonist.. There was no significant difference observed between the two groups regarding the mean number of oocytes retrieved per patient, mature metaphase II oocytes, fertilization rate, and embryo cleavage rate. Significantly higher implantation rate (21.5 vs 14.5 %) (p < 0.05), pregnancy rate (37.7 vs 23.4 %) (p < 0.05), and delivery rate (32.8 vs 20.1 %) (p < 0.05) were observed in favor of groups A compared to group B. Lower proportion of patients (4.7 %), though not statistically significant, has developed OHSS in group A compared to group B (8.4 %).. Our study shows that mild stimulation regimen is highly effective for ovarian stimulation of patients who have experienced OHSS complication without increasing the risk of OHSS.

Topics: Adult; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Prospective Studies; Recombinant Proteins

This novel study describes an effective outpatient treatment for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms.. A total of twenty-seven infertile women undergoing assisted reproductive technique with early-onset OHSS were enrolled in this non-randomized clinical trial in an academic infertility center. In all patients, after complete desensitization with long-term protocol ovarian stimulation with gonadotropins was commenced. Final oocyte maturation was triggered with human chorionic gonadotrophin. Oocytes were collected 36-38 h later using transvaginal-guided follicle aspiration under general anaesthesia. All embryos were frozen and study group patients received two consecutive doses of GnRH antagonist (Cetrotide) and the control group received daily dose of cabergoline for a week.. The research revealed that moderate and severe OHSS, hospitalization or acute care for OHSS and ascites tap were significantly lower in the antagonist (Cetrotide) group. The Patients' satisfaction with Cetrotide was noticeable. No side effect was reported in either group.. GnRH antagonists seem to be an effective outpatient treatment with rapid onset activity and minimal side effects for the management of early OHSS.

Topics: Adult; Antineoplastic Agents; Cabergoline; Ergolines; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovarian Hyperstimulation Syndrome; Pilot Projects; Young Adult

To assess the safety and efficacy of mixing cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology.. Prospective, randomized study.. An IVF center in a teaching hospital.. One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups.. In the M group, rFSH and cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and cetrorelix were administered separately.. The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability.. Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups.. Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.

Topics: Adult; Drug Combinations; Drug Therapy, Combination; Female; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies; Reproductive Techniques, Assisted

To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.. Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.. There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.. Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.

Topics: Adult; Buserelin; Contraceptives, Oral, Combined; Drug Administration Schedule; Drug Therapy, Combination; Ethinyl Estradiol-Norgestrel Combination; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Young Adult

Continuation of GnRH analogue after ovum retrieval produces a faster decline in vascular endothelial growth factor levels and ascitis in women at risk of ovarian hyperstimulation syndrome.

Topics: Adult; Ascites; Chorionic Gonadotropin; Double-Blind Method; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Luteolytic Agents; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pilot Projects; Prospective Studies; Risk Factors; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

To determine whether treatment of severe ovarian hyperstimulation syndrome (OHSS) with high-dose gonadotropin-releasing hormone (GnRH) antagonist, due to its luteolytic effect, is an effective method of management.. Six infertile patients who had been scheduled for embryo transfer and developed early-onset severe OHSS with ascites and hemoconcentration were chosen for treatment with 3.0 mg of a GnRH antagonist (Cetrotide; Cetrorelix, Serono, Madrid, Spain). The response of these patients was compared with five patients with severe early-onset OHSS who received support therapy alone. All patients were evaluated clinically, echographically, and hematologically.. Estradiol (E2) levels dropped significantly a few days after treatment. Peritoneal fluid regression measured by ultrasound was faster on the study group compared with controls. Hematocrit remained comparable in both groups during follow-up. In two cases a second bolus of GnRH-antagonist was used due to clinical and biochemical findings during the four days of observation following the initial dose. None of the patients treated with GnRH antagonists required paracentesis.. Treatment with high doses of GnRH antagonists seems to be effective in the management of severe OHSS.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovarian Hyperstimulation Syndrome; Pilot Projects

Both gonadotropin-releasing hormone (GnRH) analogs and antagonists have been used for pituitary desensitization during controlled ovarian hyperstimulation (COH). We aimed to determine the minimum effective daily dose of GnRH antagonist in women undergoing COH. We also compared the efficiency of a GnRH antagonist and a GnRH agonist.. Women undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer were divided into five groups: (1) cetrorelix 0.25 mg ( n = 86); (2) cetrorelix 0.2 mg ( n = 28); (3) cetrorelix 0.15 mg ( n = 30); (4) leuprolide acetate (LA) 0.5 mg/day ( n = 58); (5) single half-dose LA depot 1.88 mg ( n = 49). Cetrorelix was administered daily from menstrual day 8 until the day of human chorionic gonadotropin administration. LA or LA depot was started on day 21 of the previous menstrual cycle.. We observed lower gonadotropin (Gn) dosages, estradiol (E2) levels and reduced risk of ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist groups. A higher risk of luteinizing hormone (LH) surge was noted in cetrorelix 0.2 and 0.15 mg groups. Gn dosages (IU)/E2 levels (pg/mL) in each group were: (1) 1,949.4/1,191.1; (2) 1,869.6/1,010.8; (3) 1,856.7/1,023.6; (4) 2,184.5/1,323.6; and (5) 2,103.5/1,313.5, respectively. LH/OHSS risks were: (1) 3.5%/5.8%; (2) 7.1%/3.6%; (3) 13.3%/3.3%; (4) 3.4%/8.6%; and (5) 2%/8.2%, respectively. Number of oocytes/embryos/grade I, II embryos were: (1) 9.4/7.9/5.8; (2) 7.5/4.2/3.6; (3) 6.3/4.1/3.1; (4) 12.3/8.9/6.6; and (5) 11.8/8.4/6.1, respectively. There was no significant difference in terms of clinical outcomes between groups 1, 4 and 5, except for higher abortion rates (AR) in group 1. Pregnancy rate (PR)/implantation rate (IR) ratios in groups 1, 4, and 5 were statistically higher than those in groups 2 and 3. Chemical PR/IR/AR were: (1) 30.2%/5.9%/7%; (2) 21.4%/5.1%/7.1%; (3) 16.7%/4.1%/10%; (4) 32.8%/5.5%/8.6%; and (5) 30.6%/5.7%/8.2%, respectively.. The lowest effective dosage of cetrorelix for pituitary desensitization during COH luteolysis is 0.25 mg, resulting in a comparable PR but a higher AR when compared with GnRH agonist.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic

Coasting is the most popular modality for the prevention of ovarian hyperstimulation syndrome, but this procedure has not been evaluated in patients undergoing controlled ovarian hyperstimulation (COH) with GnRH antagonists. The impact of coasting in a cycle in which GnRH antagonist is used was evaluated in 29 women, and it was found that coasting did not deleteriously affect the outcome in high-responder patients undergoing COH with GnRH antagonists.

Topics: Adult; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Treatment Outcome

Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol.. 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG.. Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively).. Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Treatment Outcome

During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt.. Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E(2)) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P = 0.006). There was a statistically significant reduction in the total number of follicles with a diameter >10 mm (Wilcoxon's test; Z = 6.1; P < 0.001) and of E(2) levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P = 0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained.. Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.

Topics: Adult; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infertility, Female; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Prospective Studies; Recombinant Proteins; Risk Factors; Sperm Injections, Intracytoplasmic

To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS).. Phase III, randomized, single center study of 131 patients undergoing COS and IVF with or without ICSI, in a University affiliated Hospital. Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm. The Student's t-test, the Mann-Whitney test and the chi-square test were applied as required, using SPSS for Windows with a two-sided 5% significance level.. The mean (+/-S.D.) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group (P=0.02). The mean (+/-S.D.) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group (P<0.0001). No significant differences were noted in other outcome measures: amount of rFSH required, estradiol level on hCG day, number of follicles>or=15 mm and endometrial thickness on oocyte retrieval day, number of oocytes retrieved, fertilization rate and number of OHS cases. Clinical pregnancy rates per-attempt and per-transfer were 15.1% and 17.0% in the antagonist group and 16.9% and 20.0% in the agonist group (P=0.79 and 0.71, respectively).. GnRH antagonists are an effective, safe and well tolerated alternative to agonists for COS.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Sperm Injections, Intracytoplasmic; Treatment Outcome

Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients.. Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection.. Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols.. The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment.

Topics: Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Incidence; Infertility, Female; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Premedication

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.

Topics: Adult; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Injections, Subcutaneous; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Safety; Severity of Illness Index; Time Factors; Treatment Outcome

The objective of this study was to compare, in a centre with previous experience of gonadotrophin-releasing hormone (GnRH) antagonist use, single administration of a GnRH antagonist [cetrorelix (Cetrotide) 3 mg] with a single administration of a GnRH agonist [Decapeptyl Retard 3.75 mg] in patients undergoing assisted reproduction treatment (n = 307 and 364 respectively). GnRH agonist was administered on the first day of menses, while cetrorelix was administered when the largest follicle reached 14 mm. Ovarian stimulation was performed with recombinant human FSH (r-hFSH; 150-225 IU/day). Human chorionic gonadotrophin (HCG, 10,000 IU) was administered when at least two follicles reached a mean diameter > or =18 mm. Over 90% of patients in both groups reached the criteria for HCG administration and underwent oocyte retrieval and embryo transfer. Duration of FSH therapy (9.95 versus 11.25 days) and cumulative dose of r-hFSH (1604 versus 1980 IU) were significantly reduced (P < 0.01) in the cetrorelix 3 mg group. The number of oocytes retrieved was lower (8.5 versus 11.2; P < 0.01) with cetrorelix, but the number of embryos replaced was similar (2.2 versus 2.3; NS). The pregnancy rates per oocyte retrieval were the same, 24.5%, in the antagonist and agonist groups. This study indicates that although fewer oocytes are recovered, similar pregnancy rates can be achieved with a GnRH antagonist compared with a GnRH agonist. Additionally, a single dose of 3 mg cetrorelix was administered in 84% of patients, thus being simpler and more convenient for patients. Cetrorelix 3 mg may thus be proposed as a first choice for preventing both a premature LH surge and detrimental rises in LH during ovarian stimulation prior to assisted reproduction treatment.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Triptorelin Pamoate

To report preliminary experience in using the GnRH antagonist (Cetrotide) and to compare the multiple dose and single dose protocols.. Fifteen patients received multiple doses and another 10 patients received the single dose protocol of GnRH antagonist during ovarian stimulation for IVF treatment. Outcome measures included the duration/dosage of gonadotrophin and number of oocytes aspirated.. All patients had successful oocyte retrieval after the hCG injection. The single dose group had a significantly shorter duration of gonadotrophin but fewer frozen embryos than the multiple dose group.. Both protocols were effective in preventing premature LH surges. The stimulation regimen was simplified by reducing the total treatment period, the dosage and duration of gonadotrophin. There may be differences in ovarian responses between the two protocols.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Treatment Outcome

A total of 346 women with normal ovulatory function was stimulated with human menopausal gonadotrophins (HMG) to attain ovarian stimulation for IVF or intracytoplasmic sperm injection (ICSI). Stimulation with HMG started on cycle day 2 or 3. After 6 days of stimulation, Cetrorelix in its minimum effective multiple dose of 0. 25 mg/day, was administered daily until induction of ovulation. In total, 333 patients (96.2%) reached the day of HCG administration, and 324 (93.6%) underwent oocyte retrieval. A mean of 25.2 ampoules of HMG was applied for a mean of 10.4 days. Cetrorelix was administered for a mean time lapse of 5.7 days. The mean normal fertilization rate was 60% in the IVF group and 59% in the ICSI group. Seventy pregnancies were attained, reflecting an ongoing clinical pregnancy rate of 24% per transfer. The ongoing clinical implantation rate was 11.4%. Only three cases of raised luteinizing hormone (LH) (>/=10 IU/l) with increased progesterone secretion (>/=1 ng/ml) were observed after initiation of Cetrorelix administration, reflecting an incidence of premature luteinization of 0.9%. The abortion rate was 17%. The incidence of severe ovarian hyperstimulation syndrome (World Health Organization grade III) was as low as 0.6%.

Topics: Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies

There have been numerous double-blind, randomised, dose-finding studies of the gonadotrophin-releasing hormone (Gn-RH) antagonist Ganirelix (Org 37462) and the Gn-RH antagonist Cetrorelix.. We performed a clinical trial with 26 patients undergoing ovarian stimulation with the recombinant human follicle stimulating hormone (FSH) by applying rec. FSH in a flexible daily dose, depending on the estradiol levels of the patient, from day 3 of the cycle onwards in a controlled ovarian hyperstimulation (COH) protocol. A single dose of 0.25 mg was injected daily subcutaneously from day 7 of the cycle onwards until the day of HCG application. The recombinant FSH dose was adjusted according to ovarian response. Fifteen patients were treated for IVF and nine for ICSI. In two patients egg retrieval was not performed. Estradiol and LH levels were measured on the day of HCG application.. The mean number of recovered oocytes in the 24 patients was 5.5. A fertilisation rate of 64% was achieved in the IVF group and 69% in the ICSI group. In Germany a maximum of three embryos per patient is permitted to be transferred. Pregnancy occurred in ten patients: 5 IVF patients and 5 ICSI patients. In this small group of IVF patients a 33% pregnancy rate per follicular puncture and a 50% pregnancy rate per embryo transfer resulted. The ICSI group showed a 55% pregnancy rate per follicular puncture and a 62% pregnancy rate per embryo transfer.. Within an IVF/ET, ICSI programme the Gn-RH-antagonist Cetrorelix in combination with rec. FSH gave optimal pregnancy results.

Topics: Adult; Drug Administration Schedule; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Sperm Injections, Intracytoplasmic

A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO degrees II and degrees III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

Topics: Buserelin; Drug Administration Schedule; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Ovarian Hyperstimulation Syndrome; Prospective Studies; Reproductive Techniques

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gene Expression; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Male; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progestins; Prospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients.. Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles.. All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%).. The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation.

Topics: Adult; Cryopreservation; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Proof of Concept Study; Prospective Studies

A high dose of prolonged gonadotropins can yield higher numbers of oocytes and embryos. The high dose or prolonged regimens can be associated with ovarian hyperstimulation syndrome (OHSS), multiple gestations, emotional stress, economical burden and treatment dropout. In mild stimulation lower doses and shorter duration times of gonadotropin are used in contrast to the conventional long stimulation protocol in IVF. It has been proposed that supraphysiologic levels of hormones may adversely affect endometrium and oocyte/embryo. Also it has been proposed that oxidative stress (OS) may alter ovarian hormone dynamics and could be further affected by additional exogenous hormonal stimulation. Therefore our aim was to compare follicular fluid total antioxidant capacity (TAC) in antagonist mild and long agonist stimulations.. Forty patients received antagonist mild stimulation, starting on the 5th day of their cycle and forty patients received long agonist treatment. Seventy-five patients undergoing their first IVF cycle were included in the final analysis. Follicular fluid (FF) samples were analyzed for estradiol (E2), antimullerian hormone (AMH) and TAC.. FF-Total antioxidant capacity (TAC) levels were higher in the long agonist group as opposed to the antagonist group [1.07 ± 0.04 mmol Trolox equivalent/L vs 1 ± 0.13 mmol Trolox equivalent/L] (Fig. 1). Pregnancy rates were not significantly different between the two treatments. The FF-TAC levels were not different among infertility etiologies (Fig. 3). FF-TAC levels did not have a direct correlation with pregnancy but a positive correlation with the total gonadotropin dose was observed.. Patients with good ovarian reserves and under the age of 35 effectively responded to mild stimulation treatment. Using lower amounts of gonadotropin, yielded less FF-TAC levels in patients who underwent antagonist mild protocol. In patients under the age of 35, antagonist mild stimulation is a patient friendly and effective procedure when undergoing their first IVF cycle.

Topics: Adult; Anti-Mullerian Hormone; Antioxidants; Chorionic Gonadotropin; Embryo, Mammalian; Endometrium; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Oxidative Stress; Pregnancy; Pregnancy Rate; Recombinant Proteins

BACKGROUND The aim of this study was to compare the efficacy and safety of 2 GnRH agonists - triptorelin acetate and cetrorelix acetate - in assisted reproduction. MATERIAL AND METHODS A total of 182 females who received in vitro fertilization and embryo transfer (IVF+ET) from March 2014 to July 2014 were involved, and their clinical data were retrospectively analyzed. Among them, 91 patients received treatment with short-acting triptorelin (group A) and another 91 patients were treated with cetrorelix acetate (group B). Fasting blood was extracted from each patient on the day of administration of human chorionic gonadotropin (hCG), and serum levels of luteinizing hormone (LH), estradiol (E2), and progesterone (P) were detected using chemiluminescence method. The number of oocytes, fertilization rate, cleavage rate, and number of obtained embryos were recorded and compared. Pregnancy outcomes and adverse events were observed and compared. Expression level of FSH receptor (FSHR) in endometrial tissues was measured by qRT-PCR. RESULTS Serum level of E2 was significantly lower in group B than in group A (p<0.05). Indices, including the number of oocytes, fertilization rate and cleavage rate, number of obtained embryos, and pregnancy rate, were slightly better in group B than in group A, but no significant differences were found. The incidence of ovarian hyperstimulation syndrome (OHSS) was significant higher in group A than in group B (p<0.05). FSHR expression level was significantly lower in group B than in group A. CONCLUSIONS The effect of cetrorelix acetate is superior to that of short-acting triptorelin in assisted reproduction. Our most important finding is that cetrorelix acetate reduced the incidence of OHSS.

Topics: Adult; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Reproductive Techniques, Assisted; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

Topics: Adult; Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Menotropins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Topics: Adult; Chorionic Gonadotropin; Corpus Luteum; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Luteolysis; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate

GnRH agonist (GnRH-a) triggering is associated with a reduced risk of ovarian hyperstimulation syndrome (OHSS) compared with human chorionic gonadotropin (hCG) in assisted reproduction technology cycles. We have shown that ovarian pigment epithelium derived factor (PEDF), a potent antiangiogenic factor, counteracts vascular endothelial growth factor (VEGF) expression and that OHSS is correlated with hCG-induced impaired PEDF to VEGF ratio.. The objective of the study was to explore whether GnRH-a triggering could directly modulate PEDF/VEGF balance in granulosa cells.. The design of the study was a mouse model and cultured granulosa cells.. Changes in PEDF and VEGF were measured by quantitative PCR and Western blot analysis. OHSS symptoms were recorded by changes in body weight and in peritoneal vascular leakage, quantified by the modified Miles vascular permeability assay.. GnRH-a stimulation significantly increased PEDF and decreased VEGF mRNA and protein levels both in rat granulosa cell line and human primary granulosa cells in vitro. GnRH-a and hCG triggering inversely modulated PEDF mRNA and protein level in human granulosa cells in vivo. In the GnRH-a triggering mouse model, we showed similar increase in PEDF to VEGF ratio as in the in vitro results. OHSS-predisposed mice did not develop OHSS parameters after GnRH-a triggering, opposed to hCG-triggered mice. Finally, GnRH-a triggering of OHSS-predisposed mice significantly increased ovarian PEDF to VEGF ratio compared with hCG-triggered mice and control mice.. GnRH-a triggering induces a direct effect on PEDF/VEGF balance in granulosa cells inversely to hCG. Our results suggest a novel elucidation to the GnRH-a triggering-mediated risk reduction of OHSS and may clarify the pros and cons of this triggering method.

Topics: Adult; Animals; Cell Line; Cells, Cultured; Chorionic Gonadotropin; Eye Proteins; Female; Fertility Agents, Female; Gene Expression Regulation, Developmental; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Leuprolide; Mice, Inbred ICR; Nerve Growth Factors; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Rats; Receptors, LHRH; Serpins; Signal Transduction; Vascular Endothelial Growth Factor A; Young Adult

To determine if the GnRH antagonist protocol is effective in preventing ovarian hyperstimulation syndrome (OHSS) in potentially high responders.. A total of 660 IVF-ET/ICSI cycles were retrospectively identified. The inclusion criterion was age ≤ 30 years. Cycles were divided into two groups: a GnRHa group and a GnRHant group. In the GnRHa group, the patients received one single injection of 1.0mg-1.3mg Triptorelin in previous mid-luteal phase. In the GnRHant group, a daily dose of 0.25 mg Cetrotide was initiated when a lead follicle obtained a mean diameter of 14 mm, continued up until the day of hCG administration. The duration of stimulation, total dose of Gn, implantation rate, pregnancy rate, and OHSS rate were compared.. The duration of stimulation, E2 level on hCG day, numbers of oocytes retrieved, MII oocytes, and high-quality embryos in the GnRHa group were all significantly more than those in the GnRHant group. In the GnRHa group, 83.53% of cancelled fresh-transferred cycles were cancelled because of high risk of OHSS, which was significantly higher than that in the GnRHant group (43.55%, P<0.05). The incidence of OHSS in the GnRHa group was slightly higher than that in the GnRHant group. The implantation and clinical pregnancy rates in the GnRHa group were significantly higher than those in the GnRHant group (37.36% VS 19.25%, 62.78% VS 31.06%; P<0.05).. Our study demonstrated that for potentially high responders, the GnRHant protocol can, to some extent, lower the cancellation and incidence rates of OHSS. The GnRHa protocol was superior to the GnRHant protocol in terms of implantation and clinical pregnancy rates.

Topics: Drug Administration Schedule; Embryo Implantation; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

To investigate the kinetics of serum vascular endothelial growth factor (VEGF) following gonadotrophin-releasing hormone (GnRH) antagonist administration in the luteal phase in women with established severe early ovarian hyperstimulation syndrome (OHSS).. Pilot observational cohort study.. Private in vitro fertilisation (IVF) Unit.. Twelve IVF women diagnosed with established severe early OHSS 5 days post oocyte retrieval (POR).. Women undergoing IVF diagnosed with severe early OHSS 5 days POR were given 0.25 mg GnRH antagonist for 4 days, from day 5 until and including day 8 POR, combined with elective blastocyst cryopreservation. Serum VEGF was measured from the day of oocyte retrieval until day 11 POR. Ovarian volume, ascites, serum estradiol and progesterone, haematocrit and white blood cells were monitored during the same period.. Kinetics of VEGF following luteal GnRH antagonist administration in women with established severe early OHSS.. The concentration of VEGF was highest (390.9 ± 137.4 pg/ml) 5 days POR, coinciding with the day of diagnosis of severe OHSS. There was a significant decline of VEGF on day 7 (302.8 ± 104.9 pg/ml; P = 0.026), day 9 (303.3 ± 148.3 pg/ml; P = 0.007), and day 11 (252.6 ± 182.7 pg/ml; P = 0.010) compared with day 5 POR. This decline was associated with an improvement of ultrasound and laboratory parameters, indicating regression of severe OHSS. All women were managed at an outpatient level.. GnRH antagonist administration in the luteal phase is associated with a significant decline of VEGF and with regression of established severe early OHSS.

Topics: Adult; Cohort Studies; Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pilot Projects; Severity of Illness Index; Vascular Endothelial Growth Factor A

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of IVF cycles. Although the development of effective treatment strategies for this syndrome is important, preventing OHSS is more crucial. Triggering ovulation with a gonadotrophin-releasing hormone (GnRH) agonist is one method used to avoid OHSS. In this paper, three patients who developed severe OHSS after undergoing GnRH agonist triggering and freezing of all embryos in a GnRH antagonist protocol are described. A review of the literature is also provided. This report highlights the ongoing risk of severe OHSS even after GnRH agonist triggering combined with freezing all embryos in GnRH antagonist cycles. Other prevention strategies might be considered for extreme hyper-responders.

Topics: Adult; Chorionic Gonadotropin; Cryopreservation; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy

To determine whether inducing ovulation with a GnRH agonist in patients with polycystic ovaries (PCO) would permit oocyte retrieval without the burden or risk of cancellation, coasting, or ovarian hyperstimulation syndrome (OHSS), thus maintaining pregnancy rates by allowing embryo cryopreservation for transfer in a subsequent cycle.. Retrospective observational study.. Private institution.. Forty-two women who had previously experienced a controlled ovarian hyperstimulation (COH)/IVF cycle that had to be cancelled because of an elevated risk of OHSS.. Forty-two PCO patients with a previous cancelled IVF cycle were assigned to a second controlled ovarian stimulation with recombinant FSH (75-150 IU/day) + GnRH antagonist (0.25 mg/day). Embryos were cryopreserved and transferred in a later cycle.. OHSS, oocyte retrieval, and pregnancy rates.. In the first COH, the cycle had to be cancelled to avoid OHSS because E(2) serum levels were above safety levels (4809.6 +/- 2947.7). However, in the second cycle (ovulation triggered with a GnRH agonist) and independent of E(2) serum levels (4518.5 +/- 2118.85), all PCO patients eventually completed oocyte retrieval and frozen ET. With regard to pregnancy rates, 33% of patients receiving a transfer of a previously frozen embryo were successful. No patient developed OHSS.. Triggering ovulation with a GnRH agonist followed by embryo cryopreservation allows PCO patients to complete a COH/IVF cycle with no cycle cancellation, coasting, or OHSS and, finally, to attain good pregnancy rates.

Topics: Adult; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Recombinant Proteins; Retrospective Studies

To compare pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS) in donor stimulation cycles where final maturation of oocytes was induced with recombinant hCG or GnRH agonist.. Retrospective, cohort study.. Private infertility clinic.. A total of 1171 egg donors performing 2077 stimulation cycles.. Controlled ovarian hyperstimulation of egg donors with GnRH antagonist protocol triggered with recombinant hCG (rhCG; 250 microg) or GnRH agonist (triptorelin 0.2 mg) based on the physician's decision.. Proportion of mature and fertilized oocytes per donor cycle; clinical, ongoing pregnancy and implantation rate in recipients; and incidence of moderate/severe OHSS in oocyte donors.. The proportion of mature oocytes was comparable, whereas the difference in the fertilization rate reached statistical significance (65% vs. 69%). No significant differences were observed in the implantation rate or clinical and ongoing pregnancy rates per ET. The incidence of moderate/severe OHSS was 1.26% (13/1031; 95% confidence interval [CI], 0.74-2.15) and 0% (0/1046; 95% CI, 0.00-0.37) in the rhCG and GnRH agonist groups, respectively.. Recipient outcome was not significantly different when using oocytes from GnRH antagonist-treated donor cycles triggered with hCG or GnRH agonist. However, GnRH agonist triggering was associated with a lower incidence of moderate/severe OHSS in egg donors.

Topics: Chorionic Gonadotropin; Embryo Implantation; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Oocyte Donation; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.. Fifty patients who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (>/=4 days), and the incidences of OHSS were compared.. The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted >/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting >/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.. The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.

Topics: Adult; Clomiphene; Drug Therapy, Combination; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Sperm Injections, Intracytoplasmic; Superovulation; Treatment Outcome

There are concerns of reduced pregnancy rates with the use of gonadotrophin-releasing hormone antagonists (GnRH antagonists) in IVF/ICSI cycles. Sex steroids and their metabolizing enzymes in the endometrium may play a vital role in embryo implantation. This study has evaluated the levels and localization of sex-steroid receptors and metabolizing enzymes, 3beta-hydroxysteroid dehydrogenases (3betaHSD) and selected 17beta-HSD (17betaHSD), in mid-luteal endometrium of women treated with GnRH antagonist (Cetrorelix) and recombinant FSH (rFSH; Gonal-F) with luteal phase progesterone supplementation.. Mid-luteal phase endometrial biopsies were obtained from oocyte donors undergoing ovarian stimulation and from control women with regular periods. Immunohistochemistry and real-time quantitative-polymerase chain reaction (QRT-PCR) were used to compare protein and mRNA expression of progesterone receptor (PR), estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), androgen receptor (AR), 3betaHSD1, 3betaHSD2, 17betaHSD2 and 17betaHSD5.. Cetrorelix-rFSH treatment caused a mid-luteal suppression of PR protein expression in the endometrial stroma, surface epithelium and glands, although expression in the glands of control samples was variable. In contrast, the treatment caused an increase in PR staining in perivascular cells. No other significant differences in protein expression were observed between the two groups. mRNA levels of AR, ERalpha, 3betaHSD1 and 17betaHSD2 were significantly reduced in the treatment group. PR mRNA levels were also reduced by GnRH antagonist-rFSH treatment, but the difference was not significant.. Changes in the expression of sex-steroid receptors and metabolizing enzymes may lead to alterations in the activity and intracellular availability of estrogens, progestogens and androgens in endometrium of women treated with Cetrorelix and rFSH. Their impact on embryo implantation merits further evaluation.

Topics: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Adult; Endometrium; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Progesterone; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Sperm Injections, Intracytoplasmic

The aims of this study were to investigate whether a high dose of gonadotrophin-releasing hormone antagonist during the preceding luteal phase yields satisfactory luteolysis and downregulation prior to ovarian hyperstimulation in an in vitro fertilization program.. The treatment protocol was designed as a prospective pilot study in IVF units at two university hospitals. Fifty-one patients with documented poor or normal response to ovarian stimulation underwent 57 treatment cycles. Treatment consisted of 3 mg gonadotrophin-releasing hormone antagonist (cetrorelix) given during the preceding mid-luteal phase as gonadotrophin-releasing hormone-receptor inhibition before ovarian stimulation with follicle-stimulating hormone.. All women experienced menstrual bleeding within 2-3 days after the injection of 3 mg cetrorelix. Follicle hormone stimulation could subsequently commence in all cycles. All but three patients developed growing follicles and underwent oocyte retrieval. Seventy-five percent of started cycles reached transfer of one or two good-quality embryos.. A single high-dose gonadotrophin-releasing hormone antagonist given during the preceding luteal phase presents a new and feasible protocol to initiate controlled ovarian hyperstimulation in an in vitro fertilization program.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Embryo Transfer; Feasibility Studies; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Pregnancy; Pregnancy Rate; Prospective Studies; Risk Factors; Sensitivity and Specificity; Treatment Outcome

GnRH agonists and antagonists are utilized for avoiding premature ovulation in assisted reproductive cycles, (ART) this retrospective study was designed to compare both treatments in controlled ovarian hyperstimulation (HOC) in oocyte donors.. Between Jan99 and Mar03, 141 oocyte donors underwent ART receiving either 0.25 mg daily of a GnRH antagonist (Cetrorelix) from day 6 of stimulation (51 patients) or a long protocol with a GnRH agonist (Leuprolide acetate) (90 patients.) FSHr alone or with HMG or LHr were employed for ovarian stimulation. hCG (Profasi, Serono) was administrated when more than three follicles above 18 mm in diameter were observed, oocyte retrieval was performed 34 hours later. Embryo transfer was performed 3-5 days later.. Both groups were homogeneus for age (p=0.142), day 3 FSH (p=0.115), type and total dose of gonadotrophins utilized. There were no significant differences in follicles number (p=0.522), oestradiol levels on the day of hCG (p=0.310) and fertilization rates (p=0.177) The mean number of oocytes retrieved and metaphase II oocytes was significantly lower in GnRH agonist group, (12 vs. 13.9, p=0.05 and 8.6 vs 11; p=0.007) There was no statistical differences in pregnancy and implantation rates between agonist and antagonist groups (52.2% vs 60.8%, 15.1% vs 18.3%; p=0.327 and 0.652).. The high number of metaphase oocytes and the high pregnancy rate observed in the oocyte donors provide evidence that GnRH antagonist does not impair ovarian response, embryo quality or pregnany rates. In oocyte donors cycles the GnRH antagonist is a valid alternative to GnRH agonist, providing the benefit of more flexibility in patient's scheduling.

Topics: Adult; Embryo Implantation; Estradiol; Female; Fertility Agents, Female; Fertilization; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Leuprolide; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Retrospective Studies; Treatment Outcome