leuprolide and ganirelix

The gonadotrophin-releasing hormone antagonist ganirelix has recently become available to clinicians. Its indication, prevention of premature luteinizing hormone surges in assisted reproduction programmes, has been investigated extensively in numerous studies. This article summarizes the major results from pharmacokinetics studies, a double-blind dose-finding trial and three large-scale phase III randomized clinical trials, comparing ganirelix and the most commonly used gonadotrophin-releasing hormone agonists, buserelin,leuprolide and triptorelin, in a long protocol. It is concluded that controlled ovarian hyperstimulation with ganirelix offers significant advantages in terms of convenience of treatment as reflected in a considerably reduced treatment period.Safety and tolerance as well as overall clinical outcome are good.

Topics: Adolescent; Adult; Buserelin; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Male; Ovulation Induction; Pregnancy; Triptorelin Pamoate

The introduction of gonadotrophin-releasing hormone (GnRH) agonists combined with gonadotrophins is considered to be one of the most significant advances in the development of in vitro fertilization (IVF) treatment. However, ovarian hyperstimulation syndrome (OHSS) remains a significant complication of controlled ovarian hyperstimulation. One possible strategy to reduce the risk of this complication would be the use of GnRH agonists instead of human chorionic gonadotrophin (hCG) to trigger the final stages of oocyte maturation. GnRH agonists are able to induce an endogenous surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the effect may be more physiological than that of exogenous hCG. Several uncontrolled and controlled clinical studies have confirmed the efficacy of GnRH agonists for triggering ovulation, and pregnancy rates are comparable to those achieved with hCG. The incidence of OHSS appears to be decreased, but larger controlled studies are required to confirm this observation. The recent introduction of GnRH antagonists has led to renewed interest in the use of GnRH agonists to induce final oocyte maturation. An international multicentre randomized controlled trial has been completed recently comparing the efficacy of GnRH agonist with hCG for triggering ovulation in women undergoing controlled ovarian hyperstimulation using the GnRH antagonist ganirelix for pituitary suppression. The aim of the study was to determine the efficacy of the novel protocol for ovarian stimulation before IVF, in terms of pregnancy outcomes and the prevention of OHSS.

Topics: Chorionic Gonadotropin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Triptorelin Pamoate

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.

Topics: Administration, Cutaneous; Adult; Connecticut; Drug Administration Schedule; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Luteal Phase; Oocyte Retrieval; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Time Factors; Transdermal Patch; Treatment Outcome; Young Adult

To determine whether there are any differences in the incidence of ovarian hyperstimulation syndrome (OHSS) and implantation rates in high-risk patients undergoing IVF using a protocol consisting of GnRH agonist trigger after cotreatment with GnRH antagonist or hCG trigger after dual pituitary suppression protocol.. Prospective randomized controlled trial.. University-based tertiary fertility center.. Sixty-six patients under 40 years of age with polycystic ovarian syndrome, polycystic ovarian morphology, or previous high response undergoing IVF.. Patients were randomized to an ovarian stimulation protocol consisting of either GnRH agonist trigger after cotreatment with GnRH antagonist (study group) or hCG trigger after dual pituitary suppression with a GnRH agonist (control group). Both groups received luteal phase and early pregnancy supplementation with IM progesterone (P), and patients in the study group also received E(2) patches and their doses were adjusted according to the serum levels.. Incidence of OHSS and implantation rate.. None of the patients in the study group developed any form of OHSS compared with 31% (10/32) of the patients in the control group. There were no significant differences in the implantation (22/61 [36.0%] vs. 20/64 [31.0%]), clinical pregnancy (17/30 [56.7%] vs. 15/29 [51.7%]), and ongoing pregnancy rates (16/30 [53.3%] vs. 14/29 [48.3%]) between the study and control groups, respectively.. The use of a protocol consisting of GnRH agonist trigger after GnRH antagonist cotreatment combined with adequate luteal phase and early pregnancy E(2) and P supplementation reduces the risk of OHSS in high-risk patients undergoing IVF without affecting implantation rate.

Topics: Adult; Contraceptives, Oral, Hormonal; Embryo Implantation; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infertility, Female; Leuprolide; Luteinizing Hormone; Odds Ratio; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Risk Assessment; Sperm Injections, Intracytoplasmic; Treatment Outcome

To determine whether the use of luteal phase vaginal E(2) supplementation improves clinical pregnancy rates in patients undergoing IVF treatment.. Prospective randomized controlled trial.. University-based tertiary fertility center.. One hundred sixty-six patients undergoing their first cycle of IVF treatment.. Patients underwent three different protocols for controlled ovarian hyperstimulation for IVF treatment with long GnRH agonist suppression, use of GnRH antagonist, or a microdose GnRH agonist protocol. Luteal phase support was in the form of IM P. Patients randomized into the study group (n = 84) received E(2) supplementation in the form of vaginal estrace 2 mg twice a day starting on the day of ET. Patients randomized to the control group (n = 82) received no E(2) supplementation.. Clinical pregnancy rates.. There were no significant differences in the implantation (56/210 [26.7%] vs. 64/203 [31.5%]), clinical pregnancy (42/84 [50%] vs. 52/82 [63.4%]), and ongoing pregnancy rates (40/84 [47.6%] vs. 46/82 [56.1%]) between the study and control groups, respectively. In the subgroup of patients who used the long GnRH agonist suppression protocol, there was a lower clinical pregnancy rate in the study group compared with the control group (27/55 [49.1%] vs. 42/59 [71.2%]). There were, however, no differences in clinical pregnancy rates between the two groups in patients who used either the GnRH antagonist or microdose GnRH agonist protocols.. The addition of vaginal E(2) supplementation to routine P supplementation for luteal support does not improve the probability of conception after IVF treatment.

Topics: Administration, Intravaginal; Adult; Drug Administration Schedule; Drug Therapy, Combination; Embryo Implantation; Estradiol; Female; Fertility Agents, Female; Fertilization; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Leuprolide; Luteal Phase; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.. Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.. There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.. The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.

Topics: Adult; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Outcome

To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments.. A prospective, randomized, comparative study was conducted between January 2005 and November 2006 in a private hospital. Donors were randomized to receive a long protocol of leuprorelin + hMG (group DI) or ganirelix + rFSH (group DII). Their respective recipients were randomized to group RI or group RII, respectively.. The characteristics of the donors were similar in both groups. More cycles were cancelled in group DI than in group DII (28.1% vs. 2.5%; p < 0.05). Compared with donors in group DII, the donors in group DI required a significantly higher dose of gonadotropins (2794 +/- 957 U vs. 1777 +/- 1043 U; p < 0.05) and more days of stimulation (11.7 +/- 2.3 vs. 9.5 +/- 1.5; p < 0.05); they also yielded fewer oocytes (15.0 +/- 6.1 vs. 17.9 +/- 8.6; p < 0.05). There were no differences in the characteristics of the recipients, in the fertilization rate or in the number of embryos transferred. The quality of transferred embryos was better in group RI (8.0 +/- 1.2 vs. 7.5 +/- 1.6; p < 0.05), and this group also achieved a better pregnancy rate per embryo transfer than did group RII (62.3% vs. 48.4%; p < 0.05).. Treating oocyte donors with leuprorelin + hMG produces among recipients a greater probability of clinical pregnancy per embryo transfer than when donors are treated with ganirelix + rFSH; however, more cycles are cancelled and the former treatment is more unpleasant for donors.

Topics: Adult; Algorithms; Embryo Transfer; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Menotropins; Oocytes; Pregnancy; Pregnancy Rate; Recombinant Proteins; Tissue Donors; Transplantation

Elevated estradiol (E(2)) levels predispose to development of ovarian hyperstimulation syndrome (OHSS). Since GnRH antagonist is associated with a reduction in E(2) levels, we hypothesized that GnRH-antagonist treatment of women down-regulated with GnRH agonist who are at risk of OHSS might reduce E(2) levels and avoid cycle cancellation.. Retrospective study in a university-based assisted reproduction technology (ART) programme in 87 patients treated with long luteal (LL) or microdose flare (MDF) with ovarian hyperresponse and 87 control patients without ovarian hyperresponse. GnRH-antagonist (ganirelix acetate) treatment was started and leuprolide acetate discontinued in women who failed to respond to a reduction in gonadotrophin dosage.. In the treatment group, there was a significant, reproducible reduction in serum E(2) levels. Mean E(2) at the start of ganirelix treatment was 4219.8 pg/ml and decreased in 24 h to 2613.7 pg/ml (36.7%; P < 0.001). An average of 24.9 +/- 8.8 oocytes were obtained at retrieval and an average of 19.1 +/- 8.0 were metaphase II (79.2%). Fertilization occurred in 13.9 +/- 8.1 embryos (72.8%). In this high risk group, two cases of severe OHSS (2.3%) occurred. The ongoing pregnancy rate was 51.8%. Compared with the control group, there were no statistically significant differences in the rate of oocyte recovery, oocyte maturity, 2PN rate, fertilization, cancellation, OHSS or pregnancy.. GnRH-antagonist treatment of women pretreated with GnRH agonist rapidly reduced circulating serum E(2) without adversely affecting oocyte maturation, fertilization rates or embryo quality and resulted in a high pregnancy rate in this subgroup of patients at risk of OHSS.

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Fertilization; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Outcome; Reference Values; Retrospective Studies

To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day.. Prospective, randomized, multicenter study.. Private practice and university centers.. Eighty patients undergoing IVF who met the appropriate inclusion criteria.. Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered.. The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate.. Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups.. The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.

Topics: Adult; Appointments and Schedules; Contraceptives, Oral, Combined; Desogestrel; Drug Combinations; Drug Therapy, Combination; Ethinyl Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovarian Follicle; Pregnancy; Pregnancy Outcome; Prospective Studies

Forty-eight patients who met the criteria of poor response during prior gonadotropin stimulation were enrolled in a randomized prospective study comparing a gonadotropin-releasing hormone (GnRH) antagonist protocol, using ganirelix acetate, with a microdose GnRH agonist protocol for in vitro fertilization-embryo transfer (IVF-ET). This pilot study contributes to the literature of poor response IVF treatment protocols because the use of ganirelix appears to be as effective as the microdose protocol and may be a superior choice in terms of cost and convenience for the patient.

Topics: Adult; Chi-Square Distribution; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pilot Projects; Pregnancy; Prospective Studies

To compare outcome following in vitro fertilization-embryo transfer (IVF-ET) using controlled ovarian hyperstimulation (COH) regimens using either the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate vs the GnRH antagonist ganirelix.. Women needing IVF for conception were randomly assigned to 300 IU of gonadotropins with ganirelix used in the follicular phase when a follicle with a 14 mm average diameter was attained vs a regimen using leuprolide acetate from the mid-luteal phase of the previous cycle.. There were no differences found in clinical, ongoing, delivered pregnancy rates or implantation rates between groups.. The use of GnRH antagonists do not seem to reduce IVF outcome compared to using GnRH agonists in COH regimens.

Topics: Adult; Dose-Response Relationship, Drug; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, beta Subunit; Follicular Phase; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Luteal Phase; Menotropins; Pregnancy; Pregnancy Rate; Prospective Studies

To determine the effects of controlled ovarian hyperstimulation and resultant high levels of E(2) on endometrial HOXA10 expression (a marker of endometrial receptivity).. Prospective study.. University academic medical center.. Twenty-five women undergoing controlled ovarian hyperstimulation with recombinant FSH and 30 fertile controls.. Endometrium was obtained by Pipelle endometrial biopsy on cycle days 21-25. In addition, Ishikawa cells (a well-differentiated endometrial adenocarcinoma cell line) were treated with either E(2), recombinant FSH, GnRH agonist, or GnRH antagonist. RNA was extracted and analyzed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).. HOXA10 expression.. Endometrial HOXA10 expression in women undergoing controlled ovarian hyperstimulation (COH) with recombinant FSH was not different from that in fertile controls. Estradiol increased HOXA10 expression in Ishikawa cells in a dose-dependent manner from 10(-9) to 10(-7) M. Neither recombinant FSH, GnRH agonist, nor GnRH antagonist altered HOXA10 expression in these cells.. Controlled ovarian hyperstimulation did not inhibit endometrial HOXA10 expression in vivo. In addition, in vitro endometrial cell HOXA10 expression was not altered by either recombinant FSH, GnRH agonist, or GnRH antagonist. COH is unlikely to adversely impact endometrial receptivity.

Topics: Adult; Embryo Implantation; Endometrium; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Homeobox A10 Proteins; Homeodomain Proteins; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Prospective Studies; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tumor Cells, Cultured

To investigate hCG and insulin-stimulated progesterone (P) production by human granulosa-lutein cells (hGLC) in vitro.. hGLCs were isolated from patients undergoing IVF-ET cycles in which GnRH agonist or GnRH antagonist was used to prevent a midcycle gonadotropin surge. The cells were cultured for 3 days, and then treated with hCG 0.5, 1, and 10 IU/I, and insulin 0.01, 0.1, and 1 microM in serum free conditions. In vitro P production was measured by enzyme immunoassay.. hCG stimulated P production by hGLCs from cycles in which GnRH antagonist was used, but a blunted response was seen in GnRH-agonist treated cycles. Insulin-stimulated P production was similar in cells from cycles in which GnRH-agonist or GnRH-antagonist treatment was used.. Because insulin and hCG may share common pathways beyond the level of receptor activation, we hypothesize that GnRH agonist, but not GnRH antagonist, may affect the expression and/or activation of LH receptors in the hGLCs.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Insulin; Leuprolide; Luteal Cells; Ovulation Induction; Progesterone

In a randomized multicenter study, the efficacies of two different GnRH agonists were compared with that of hCG for triggering final stages of oocyte maturation after ovarian hyperstimulation for in vitro fertilization. Ovarian stimulation was conducted by recombinant FSH (Puregon), and the GnRH antagonist ganirelix (Orgalutran) was coadministered for the prevention of a premature LH rise. Luteal support was provided by daily progestin administration. Frequent blood sampling was performed at midcycle in the first 47 eligible subjects included in the current study, who were randomized for a single dose of 0.2 mg triptorelin (n = 17), 0.5 mg leuprorelin (n = 15), or 10,000 IU hCG (n = 15). Serum concentrations of LH, FSH, E2, and progesterone (P) were assessed at variable intervals. LH peaked at 4 h after both triptorelin and leuprorelin administration, with median LH levels of 130 and 107 IU/liter (P < 0.001), respectively. LH levels returned to baseline after 24 h. Subjects receiving hCG showed peak levels of 240 IU/liter hCG 24 h after administration. A rise in FSH to 19 IU/liter (P < 0.001) was noted in both GnRH agonist groups 8 h after injection. Within 24 h the areas under the curve for LH and FSH were significantly higher (P < 0.001) in both GnRH agonist groups compared with that for hCG. E2 and P levels were similar for all groups up to the day of oocyte retrieval. Luteal phase areas under the curve for P and E2 were significantly elevated (P < 0.001) in the hCG group. The mean (+/-SD) numbers of oocytes retrieved were 9.8 +/- 5.4, 8.7 +/- 4.5, and 8.3 +/- 3.3; the percentages of metaphase II oocytes were 72%, 85%, and 86%; and fertilization rates were 61%, 62%, and 56% in the triptorelin, leuprorelin, and hCG group, respectively (P = NS for all three comparisons). These findings support the effective induction of final oocyte maturation in both GnRH agonist groups. In summary, after treatment with the GnRH antagonist ganirelix for the prevention of premature LH surges, triggering of final stages of oocyte maturation can be induced effectively by a single bolus injection of GnRH agonist, as demonstrated by the induced endogenous LH and FSH surge and the quality and fertilization rate of recovered oocytes. Moreover, corpus luteum formation is induced by GnRH agonists with luteal phase steroid levels closer to the physiological range compared with hCG. This more physiological approach for inducing oocyte maturation may represent a successful and safe

Topics: Adult; Cellular Senescence; Chorionic Gonadotropin; Endocrine Glands; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Leuprolide; Oocytes; Ovary; Treatment Outcome

To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH).. Phase III, multicenter, open-label randomized trial.. In vitro fertilization (IVF) centers in North America.. Healthy female partners (n = 313) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated.. Patients were randomized to receive one COH cycle with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection.. Number of oocytes retrieved, pregnancy rates, endocrine variables, and safety variables.. The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62.4% and 61.9% in the ganirelix and leuprolide groups, respectively, and implantation rates were 21.1% and 26.1%. Clinical and ongoing pregnancy rates per attempt were 35.4% and 30.8% in the ganirelix group and 38.4% and 36.4% in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11.9% and 0.6%) than with leuprolide (24.4% and 1.1%).. Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Double-Blind Method; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovary; Pregnancy; Progesterone; Prospective Studies; Recombinant Proteins; Stimulation, Chemical

Topics: Adult; Chorionic Gonadotropin; Combined Modality Therapy; Female; Fertility Agents, Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Living Donors; Menotropins; Nephrectomy; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Renal Insufficiency; Severity of Illness Index; Treatment Outcome

No significant differences in outcomes have been found between protocols of endometrial preparation for frozen embryo transfer (FET), though gonadotropin releasing hormone (GnRH) antagonists may have detrimental effects on the endometrium. We conducted a retrospective cohort noninferiority study at a single academic center of women receiving multiple doses of mid-cycle GnRH antagonist (GAnt) to those receiving GnRH agonist (GAg) to determine if there are detrimental effects of GnRH antagonists. 1047 FET cycles were identified, detailed data was available in 840 cycles: 610 GAg and 230 GAnt cycles. Patients undergoing GAnt cycles were older (40 ± 6.6 versus 37 ± 5.1 years, p < 0.0001), more often used donor oocyte (36% versus 18.6%, p < 0.0001), and more often exhibited diminished ovarian reserve (49.1% versus 36.2%, p = 0.0009). Clinical pregnancy rates (CPRs) per transfer and implantation rates (IRs) were similar for GAnt and GAg cycles. There was a trend for higher pregnancy and IRs with GAg cycles in younger women (CPR 38.8% versus 26.7%, p = 0.16; IR 36% versus 23.3%, p = 0.07). Stratifying by diagnosis, CPR and IR were similar in GAnt and GAg cycles. A GAnt protocol of endometrial preparation for FET is not inferior to a GAg protocol regardless of patient age, use of donor oocyte, or infertility diagnosis.

Topics: Adult; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies

The aim of the presented study is to investigate the impact of progesterone change in the late follicular phase on the pregnancy rates of both agonist and antagonist protocols in normoresponders.. A total of 201 normoresponder patients, who underwent embryo transfer were consecutively selected. 118 patients were stimulated using a long luteal GnRH agonist protocol and 83 using a flexible antagonist protocol. The level of change in late follicular phase progesterone was calculated according to the progesterone levels on the hCG day and pre-hCG day (1 or 2 days prior to hCG day) measurement.. Clinical pregnancy rates were comparable between long luteal and antagonist group (35.6 and 41%, respectively). The incidence of progesterone elevation on the hCG day was 11% in long luteal and 18% in antagonist group (p = 0.16). In pregnant cycles, p levels both on the hCG day and pre-hCG day measurement were significantly higher in antagonist than agonist cycles (p = 0.029, p = 0.038, respectively). The change of p level was statistically significant in non-pregnant cycles both for the agonist (-0.17 ± 0.07; 95% CI: -0.29 to -0.37) and antagonist groups (-0.18 ± 0.07; 95%CI: -0.31 to -0.04).. Late follicular phase progesterone levels were stable during the cycles of pregnant patients irrespective of the protocols and were shown to be higher in pregnant patients in antagonist cycles when compared to agonist cycles.

Topics: Adult; Case-Control Studies; Embryo Transfer; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Luteinizing Hormone; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Sperm Injections, Intracytoplasmic

The aim of this study was to evaluate whether dual trigger with leuprolide acetate plus recombinant human chorionic gonadotropin (hCG) improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles.. A total of 156 patients diagnosed with mild male factor, unexplained or tubal factor infertility were enrolled in the study. All subjects were allocated into one of two groups: the dual trigger group (leuprolide acetate 500 μg + recombinant hCG 250 μg) and the standard group (recombinant hCG 250 μg) according to the selected trigger method. Oocyte trigger was performed when at least three follicles >17 mm were observed. Pregnancy rate, number of collected oocytes, number of metaphase II oocytes, number of grade-A embryos, cycle cancellation rate, and ovarian hyperstimulation syndrome rate were the main outcome measures for the study.. The mean number of grade-A embryos (1.6 ± 1.5 vs 1.1 ± 1.4, P = 0.01) and of metaphase II oocytes (7.9 ± 4.6 vs 6.3 ± 5.8, P = 0.02) was significantly higher in the dual-trigger group. Pregnancy rate was significantly higher in the dual-trigger group than in the standard group (54.8 vs 37.5%, P = 0.006). Two cases of mild ovarian hyperstimulation syndrome were observed in each group.. This novel and more physiological trigger approach using 500 μg leuprolide acetate plus 250 μg recombinant hCG may lead to an increase in the number of metaphase II oocytes, grade-A embryos, and may improve pregnancy rates.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Metaphase; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins

To evaluate the effects of a gonadotropin-releasing hormone (GnRH) antagonist protocol, with or without oral contraceptive pill (OCP) pretreatment, in patients with polycystic ovary syndrome (PCOS) undergoing intracytoplasmic sperm injection (ICSI).. In this retrospective cohort study, 410 infertile patients with PCOS were assessed in their first ICSI cycles between January 2006 and June 2013. In Group A (n=208), patients underwent a long luteal GnRH agonist protocol, and in Groups B (n=143) and C (n=59), patients underwent a GnRH antagonist protocol. The patients in Group C also received OCPs containing 30mg of ethinyl oestradiol and 3mg of drospirenone prior to treatment. The main outcome measures were pregnancy and ovarian hyperstimulation syndrome (OHSS) rates.. Demographic features, body mass index, duration of infertility, serum baseline hormone levels, cycle outcomes, multiple pregnancy rates, miscarriage rates, OHSS rates, total number of Grade A embryos and total number of transferred embryos were comparable between the groups. Clinical pregnancy rates were 27.4%, 26.6% and 23.7% in Groups A, B and C, respectively (p=0.853).. OCP pretreatment was found to have no beneficial or adverse effects in patients with PCOS undergoing a GnRH antagonist protocol for ICSI, but can be used for cycle scheduling.

Topics: Adult; Androstenes; Cohort Studies; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Administration Schedule; Drug Therapy, Combination; Embryo Transfer; Ethinyl Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

Are there factors predicting the number of total and mature oocytes retrieved after controlled ovarian hyperstimulation (COH) utilizing a gonadotropin-releasing hormone (GnRH) antagonist protocol and a GnRH agonist (GnRHa) to induce oocyte maturation?. Peak estradiol (E₂) level, post-trigger LH and progesterone and the magnitude of LH rise are independent predictors of the total number of oocytes and mature oocytes retrieved.. Despite multiple follicular development in high responders, oocyte retrieval after a GnRHa trigger in a small subset of patients fails to obtain a substantial number of total oocytes or mature oocytes.. A retrospective chart review of all autologous and oocyte donation cycles utilizing a GnRHa antagonist protocol where GnRHa was used for the induction of oocyte maturation between 1 April 2003 and 31 December 2011.. A total of 508 autologous and donor IVF/ICSI cycles utilizing a GnRH antagonist protocol for COH and GnRHa for the induction of oocyte maturation at a university-based tertiary fertility center.. Peak E₂ on the day of trigger (r = 0.19, P < 0.001), post-trigger LH (r = 0.12, P = 0.009) and progesterone (r = 0.47, P < 001) and LH rise (r = 0.18, P < 0.001) all positively correlated with the number of total and mature oocytes retrieved. The true incidence of empty follicle syndrome was 1.4% (7/508). There was no post-trigger LH or progesterone cut-off value for the prediction of oocyte yield. However, all cases of empty follicle syndrome occurred in patients with post-trigger LH <15 IU/l and P ≤ 3.5 ng/ml. The findings of this study may also be due to chance since it was a retrospective study and not prospectively designed.. This is a retrospective chart review and therefore subject to bias. Serum hormone measurements were performed between 8 and 12 h after GnRHa trigger rather than a standardized time period following trigger administration. Therefore, peak levels of LH may have been missed due to the short ascending limb of LH rise lasting approximately 4 h after GnRHa trigger.. The results of this study can be generalized to high responders utilizing a GnRH antagonist protocol for COH and a GnRHa for the induction of oocyte maturation. The use of alternative stimulation regimens or medications will limit the ability to generalize the results of this study to other populations.. This study was not funded, and there are no conflicts of interest.. n/a.

Topics: Biomarkers; Electronic Health Records; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Luteinizing Hormone; Models, Biological; Oocyte Donation; Oogenesis; Ovary; Ovulation Induction; Progesterone; Retrospective Studies; Sperm Injections, Intracytoplasmic

To compare pregnancy rates following the transfer of thawed frozen embryos according to the type of GnRH antagonist or agonist used during controlled ovarian hyperstimulation (COH).. Retrospective review of frozen embryo transfers according to whether a GnRH agonist or antagonist was used. Furthermore to determine if a specific antagonist/agonist resulted in higher pregnancy rates than the other.. The pregnancy rates in two different age categories were similar whether the COH regimen used the GnRH agonist leuprolide acetate or the GnRH antagonist cetrorelix. However, lower pregnancy rates were found with the GnRH antagonist ganirelix.. These data reached similar conclusions as was found comparing these three agents in fresh embryo transfer.

Topics: Adult; Embryo Transfer; Endometrium; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Outcome; Retrospective Studies

This study investigated whether follicular fluid (FF) and serum (S) concentrations of cytokines in women undergoing assisted reproductive treatment (ART) were different in GnRH antagonist cycles compared to agonist long ones.. A retrospective clinical study was performed at a University ART center. A total of 85 women who underwent ART either with agonist long (n = 34) or antagonist protocol (n = 51) were analyzed. FF and serum samples were collected at the time of oocyte retrieval and measured for interleukin (IL)- 1beta, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-alpha by the enzyme-linked immunosorbent assay (ELISA) technique, using commercially available kits and nitric oxide (NO) by the nitrate/nitrite colorimetric assay. The results were compared between GnRH antagonist and agonist cycles.. No significant difference was found in the FF concentrations of those cytokines between the two protocols. The serum values were also similar in the two groups except IL-6 (14.3 +/- 4.8 vs. 20.5 +/- 12.2 pg/ml; p = 0.008) and NO (1.4 +/- 1.1 vs. 2.2 +/- 1.9 microm; p = 0.038) levels which were found to be significantly lower in antagonist cycles.. There is no significant difference in follicular microenvironment in terms of IL-1beta, IL-6, IL-8, IL-12, TNF-alpha, and NO levels between agonist long and antagonist cycles. However, serum IL-6 and NO levels were lower in women given antagonists.

Topics: Adult; Cytokines; Female; Fertility Agents, Female; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Reproductive Techniques, Assisted; Retrospective Studies

This study evaluated women with a high body mass index (BMI) (>40 kg/m(2)) and low BMI (<18 kg/m(2)) undergoing assisted reproduction treatment and determined whether the type of gonadotrophin-releasing hormone (GnRH) analogue used has an impact on cycle parameters and outcome. The study analysed 65 women with high BMI and 118 with low BMI. In the former group, polycystic ovarian syndrome was significantly more prevalent in the agonist long protocol (ALP) group (P=0.01) and gonadotrophin consumption was lower, peak oestradiol concentrations and total number of oocytes retrieved were higher in the ALP group compared with the antagonist (ANT) group. Implantation rate (IR), pregnancy rate (PR) per embryo transfer and early pregnancy loss rate (EPLR) were similar in both stimulation groups, with overall rates of 21.6%, 55.4% and 44.4%, respectively. In women with low BMI, peak oestradiol concentrations, total oocytes retrieved, mature oocytes and transferred embryos were higher in the ALP group compared with ANT group. IR, PR/embryo transfer and EPLR were similar in both groups, with overall rates of 24.3%, 52.5% and 16.1%, respectively. In all patients, no difference was found between ALP and ANT protocols concerning treatment outcome. Contrary to the reasonable EPLR observed in women with low BMI, the high rate found in women with high BMI is remarkable.

Topics: Abortion, Spontaneous; Adult; Body Mass Index; Embryo Implantation; Embryo Transfer; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies

We examined whether Gonadotrophin-releasing hormone (GnRH) analogues [leuprolide acetate (LA) and ganirelix acetate (GA)] modulate gene expression in Ishikawa cells used as surrogate for human endometrial epithelial cells in vitro. The specific aims were: (i) to study the modulatory effect of GnRH analogues by RT-PCR [in the absence and presence of E(2) and P4, and cyclic adenosine monophosphate (cAMP)] on mRNA expression of genes modulated during the window of implantation in GnRH analogues/rFSH-treated assisted reproductive technology cycles including OPTINEURIN (OPTN), CHROMATIN MODIFYING PROTEIN (CHMP1A), PROSAPOSIN (PSAP), IGFBP-5 and SORTING NEXIN 7 (SNX7), and (ii) to analyze the 5'-flanking regions of such genes for the presence of putative steroid-response elements [estrogen-response elements (EREs) and P4-response element (PREs)]. Ishikawa cells were cytokeratin+/vimentin- and expressed ERalpha, ERbeta, PR and GnRH-R proteins. At 6 and 24 h, neither LA nor GA alone had an effect on gene expression. GnRH analogues alone or following E(2) and/or P4 co-incubation for 24 h also had no effect on gene expression, but P4 significantly increased expression of CHMP1A. E(2) + P4 treatment for 4 days, alone or followed by GA, had no effect, but E(2) + P4 treatment followed by LA significantly decreased IGFBP-5 expression. The addition of 8-Br cAMP did not modify gene expression, with the exception of IGFBP-5 that was significantly increased. The GnRH analogues did not modify intracellular cAMP levels. We identified conserved EREs for OPN, CHMP1A, SNX7 and PSAP and PREs for SNX7. We conclude that GnRH analogues appear not to have major direct effects on gene expression of human endometrial epithelial cells in vitro.

Topics: Analysis of Variance; Carrier Proteins; Cell Cycle Proteins; Cells, Cultured; Endometrium; Endosomal Sorting Complexes Required for Transport; Epithelial Cells; Estradiol; Estrogens; Female; Fertility Agents, Female; Gene Expression; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 5; Leuprolide; Membrane Transport Proteins; Progesterone; Progestins; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Saposins; Sorting Nexins; Transcription Factor TFIIIA; Vesicular Transport Proteins

To determine if controlled ovarian hyperstimulation (COH) regimens using the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate result in higher pregnancy and implantation rates than COH regimens using the GnRH antagonists cetrorelix or ganirelix following fresh and frozen embryo transfer.. Retrospective analysis was performed evaluating the pregnancy rates with the first fresh and first frozen embryo transfer cycles according to which protocol was used. A haphazard decision was made on which protocol to use. Women were required to be < 40 years of age and have had > or = 5 eggs retrieved.. Significantly lower implantation rates were seen with ganirelix compared to leuprolide acetate or cetrorelix.. These data should hopefully encourage interest in a prospective study to determine if conclusions about the inferiority of ganirelix are not merely fortuitous.

Topics: Adult; Cryopreservation; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Pregnancy; Pregnancy Rate; Retrospective Studies

In young women, estradiol and progesterone primarily control reproduction, but they also affect fluid regulation. Estradiol lowers the operating point for osmoregulation of arginine vasopressin and thirst and increases plasma volume. Although total body water and sodium content are only mildly affected, data presented in this article suggest that reproductive hormones alter homeostatic set points for body fluid and tonicity.

Topics: Arginine Vasopressin; Body Fluids; Estradiol; Female; Gonadotropin-Releasing Hormone; Homeostasis; Humans; Leuprolide; Male; Progesterone; Saline Solution, Hypertonic; Sodium; Thirst; Water-Electrolyte Balance

HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of GnRH antagonists on endometrial receptivity, we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles.. Prospective case-control study.. University academic medical center.. Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation with recombinant FSH and used either a GnRH antagonist or a GnRH agonist; seven control subjects underwent natural cycles.. Pipelle endometrial biopsies were obtained 11 days after hCG administration or spontaneous LH surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma.. Endometrial HOXA10 protein expression.. HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist-treated cycles compared with GnRH agonist-treated cycles or natural cycle control subjects. There was no significant difference in glandular cell HOXA10 expression among the three groups.. Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells and thus may affect endometrial receptivity.

Topics: Adult; Biopsy; Case-Control Studies; Endometrium; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Homeobox A10 Proteins; Homeodomain Proteins; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Prospective Studies; RNA, Messenger; Stromal Cells

Forty-seven patients at high risk for ovarian hyperstimulation syndrome because of markedly elevated serum E2 levels on either long-luteal or microdose flare leuprolide acetate regimens were treated with ganirelix acetate. Despite being pretreated with GnRH agonist and without withholding gonadotropins, serum E2 decreased by 49.5% and 41.0% of pretreatment values (long luteal and microdose flare, respectively) after initiation of ganirelix, and 68.1% of the patients became pregnant.

Topics: Adult; Cohort Studies; Estrogens; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Risk Factors

To compare the clinical outcome of controlled ovarian hyperstimulation (COH) in unselected patients undergoing IVF using multidose ganirelix acetate versus 4 days of administration of leuprolide acetate.. Retrospective cohort study.. A fertility and IVF center.. Two hundred forty-seven women who underwent COH-IVF between April 1, 1999, and January 30, 2001.. Pituitary suppression according to a 4-day follicular phase leuprolide acetate protocol (236 women) or a multidose ganirelix acetate regimen (133 women).. Amount of gonadotropin used, days of stimulation, cancellation rate, number of oocytes retrieved, implantation rate, and clinical pregnancy rate.. Compared with leuprolide acetate recipients, ganirelix recipients required significantly less gonadotropin and the mean day of hCG administration was 4 days earlier. Among women younger than 35 years of age, the implantation rate (15% vs. 6%) and the clinical pregnancy rate per initiated and transferred cycle (27% vs. 12% and 32% vs. 15%, respectively) were significantly higher in the ganirelix group than the leuprolide acetate group.. Compared with a 4-day leuprolide acetate protocol, COH-IVF using a multidose ganirelix acetate protocol reduces treatment duration and amount of gonadotropin used. In younger women, the latter protocol is associated with significantly better pregnancy and implantation rates.

Topics: Adult; Cohort Studies; Drug Administration Schedule; Embryo Implantation; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Linear Models; Luteinizing Hormone; Multivariate Analysis; Ovulation Induction; Pregnancy; Progesterone; Retrospective Studies; Time Factors

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Luteinizing Hormone; Male; Oocytes; Pregnancy; Pregnancy Outcome; Progesterone; Sperm Injections, Intracytoplasmic

Topics: Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Ovulation Induction; Randomized Controlled Trials as Topic; Statistics as Topic

Topics: Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovulation Induction; Randomized Controlled Trials as Topic; Statistics as Topic