leuprolide and Ovarian-Hyperstimulation-Syndrome

The purpose of this review is to analyze current medical strategies in the prevention\ of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation for in vitro fertilization.\ Owing to contemporary preventive measures of OHSS, the incidence of moderate and severe\ forms of the syndrome varies between 0.18% and 1.40%. Although none of medical strategies is\ completely effective, there is high-quality evidence that replacing human chorionic gonadotropin\ (hCG) by gonadotropin-releasing hormone (GnRH) agonists after GnRH antagonists and moderate-\ quality evidence that GnRH antagonist protocols, dopamine agonists and mild protocols reduce\ the occurrence of OHSS. Among various GnRH agonists, buserelin 0.5 mg, triptorelin 0.2 mg and\ leuprolide acetate (0.5-4 mg) have been mostly utilized. Although GnRH trigger is currently regarded\ as the best tool for OHSS prevention, intensive luteal support with exogenous administration\ of estradiol and progesterone or low-dose hCG on the day of oocyte retrieval or on the day of GnRH\ agonist trigger are required to achieve optimal conception rates due to early luteolysis. Among currently\ available dopamine agonists, cabergoline, quinagolide and bromocriptine are the most common\ drugs that should be used for prevention of both early and late OHSS. Mild stimulation protocols\ offer attractive option in OHSS prevention with satisfactory pregnancy rates.

Topics: Aminoquinolines; Bromocriptine; Buserelin; Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Estrogens; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; 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

To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature.. Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications.. In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS.. Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.

Topics: Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Triptorelin Pamoate

Although the use of luteinizing hormone-releasing hormone (LHRH) agonists and human menopausal gonadotropin (hMG) for ovarian stimulation in assisted reproduction has gained widespread popularity, a number of major issues regarding their use remain unresolved. Some of these issues are examined in the light of recent developments. The routine use of LHRH agonists produces significantly higher pregnancy and livebirth rates compared with conventional methods of ovarian stimulation. A number of prospective, randomized studies have shown that the long protocol of LHRH agonist administration is superior to the short and ultrashort protocols, and it appears that early follicular phase initiation of the long protocol may be particularly beneficial. Another major advantage of the long protocol of LHRH agonist administration is that, with its use, precise timing of human chorionic gonadotropin (hCG) administration is not important. It would, therefore, appear that the routine use of LHRH agonists has both medical as well as practical advantages.

Topics: Abortion, Spontaneous; Clinical Protocols; Drug Administration Schedule; Drug Therapy, Combination; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors

To determine the effects of addition of different dosages of gonadotrophin releasing hormone agonist (GnRH-a) to routine luteal phase support (LPS) on implantation and pregnancy rates.. Three hundred infertile couples who were treated by intracytoplasmic sperm injection and embryo transfer (ICSI-ET) following controlled ovarian stimulation (COS) with long luteal GnRH agonist protocol were enrolled. All women received 600 mg/day vaginal micronized progesterone plus 4 mg 17β estradiol for LPS starting from the day of oocyte retrieval. Patients (n=300) were randomized into three treatment groups. Group A (n=100) received leuprolide acetate 1 mg s.c. injection 3 days after ET in addition to routine LPS. Group B (n=100) received two sequential doses of leuprolide acetate 1 mg s.c. injections 3 and 6 days after ET in addition to routine LPS. Control group (n=100) received only the routine LPS.. A total of 279 patients completed the study. The groups were comparable in terms of baseline demographic parameters including age, duration of infertility and day 3 levels of FSH and estradiol. The cycle parameters of the groups were also comparable regarding the E2 level on day of hCG, number of retrieved oocytes, number of day 3 embryos, number of embryos transferred, and endometrial thickness on both days of OPU and ET. The implantation rates were similar in between the Groups A, B, and control group (20.7% and 25.8% vs. 13.3%, respectively; P=.099). The clinical pregnancy rates and miscarriage rates were similar in between the groups. The ongoing pregnancy rates were 27.4% in control group, 36% in Group A and 42.9% in Group B (P=.093). The OHSS rates were comparable in between the groups. The multiple pregnancy rates were significantly higher in Groups A and B than in control group (12% and 17.9% vs. 4.2%, respectively; P=.014).. The implantation, clinical pregnancy and ongoing pregnancy and multiple pregnancy rates seem to be increased with the addition of GnRH-a to routine luteal phase support.

Topics: Abortion, Spontaneous; Adult; Embryo Implantation; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteal Phase; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Progesterone; Prospective Studies; Sperm Injections, Intracytoplasmic; 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

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

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

Gonadotrophin-releasing hormone agonist (GnRHa)-induced ovulation after gonadotrophin ovarian stimulation is used to prevent ovarian hyperstimulation syndrome and multiple pregnancy in polyfollicular cycles. However, one of the major problems to be resolved is corpus luteum function after follicular maturation and ovulation by mid-cycle GnRHa administration. The present report investigated the luteal phase in non-conceptual polyfollicular cycles in 26 patients (group 1) receiving a single dose of 0.5 mg leuprolide acetate to induce ovulation and in a control group of patients (n = 26) (group 2) who were given human chorionic gonadotrophin (HCG) (10,000 IU i.m.) for ovulation induction. All of them were normal ovulatory women undergoing gonadotrophin ovarian stimulation because of unexplained infertility or male factor. In both groups of patients two doses of 2500 IU HCG i.m. were given 6 and 10 days after the ovulatory dose of HCG or GnRHa to support the luteal phase. All cycles were ovulatory as shown by mid-luteal serum progesterone concentrations >10 ng/ml. Mean serum progesterone concentrations were 62% higher in group 2 than in group 1, but this difference was not statistically significant. The mean length of the luteal phase was similar in groups 1 and 2. It is concluded that HCG luteal support is a useful tool to overcome the luteal phase inadequacy that characterizes GnRHa-triggered cycles after gonadotrophin stimulation.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Injections, Intramuscular; Leuprolide; Luteal Phase; Male; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Prospective Studies

The purpose of the present study was (i) to assess the value of using a low dose of hMG (75 IU/day) to achieve ovarian stimulation in women who have previously shown an exaggerated response to a standard dose of 150 IU human menopausal gonadotropin/day in a desensitization (group I) or flare-up (group II) protocol and (ii) to determine whether the choice of GnRH-a regimen in a subsequent cycle, namely, a desensitization or flare-up protocol, influenced the effectiveness of the low dose of hMG.. In group I, 75% (12/16) and 57% (8/14) of the subsequent desensitization and flare-up protocols, respectively, were cancelled because of inadequate ovarian response. Similarly, the cancellation rates in group II were 10 of 10 and 7 of 11 (64%), respectively. The total cancellation rate (groups I and II together) with the desensitization protocol was higher than that using the flare-up protocol (P < 0.05).. The simple use of a reduced dose of hMG (75 IU/day) for subsequent in vitro fertilization in women to minimize the risk of the development of ovarian hyperstimulation is of limited benefit since a large proportion then shows an inadequate response. This is particularly pronounced with a subsequent desensitization protocol which does not utilize endogenous gonadotropins to initiate follicular development.

Topics: Adult; Buserelin; Dose-Response Relationship, Drug; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Gonadotropins; Humans; Leuprolide; Menotropins; Menstrual Cycle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Radioimmunoassay; Risk Factors

Three long protocols of ovarian stimulation for IVF using long acting GnRH agonist and hMG were compared. 3 molecules were used: Triptoreline (Décapeptyl* 3.75 mg), gosereline (Zoladex*) and leuproreline (Enantone* 3.75 mg). Assigning of these 3 protocols were randomised. 63, 68 and 67 cycles of stimulation were studied. Results in term of pregnancy are the same in the 3 groups. Only a tendency of lower frequency of ovarian hyperstimulation in Décapeptyl 3.75 mg group is found, associated with less embryo and less cycles with cryopreservation of supernumeraries embryos (p = 0.1).

Topics: Adult; Clinical Protocols; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fertilization in Vitro; Goserelin; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Triptorelin Pamoate

To report three cases of severe ovarian hyperstimulation syndrome (OHSS) among oncofertility patients receiving a long-acting GnRH agonist for ovarian suppression after controlled ovarian hyperstimulation (COH) with a GnRH antagonist protocol METHODS: Chart abstraction was completed for three patients at a single academic medical center. Patients included were undergoing fertility preservation prior to gonadotoxic chemotherapy. All patients underwent COH with GnRH antagonist protocol and embryo cryopreservation immediately followed by ovarian suppression with long-acting GnRH agonist. Main outcome measure was development of OHSS.. Despite using GnRH agonist trigger and freezing all embryos, patients developed ascites, intermittent hyponatremia and hemoconcentration consistent with severe early-onset OHSS after receiving long-acting GnRH agonist immediately following oocyte retrieval for ovarian preservation.. Risk of severe OHSS may be increased when a long-acting GnRH agonist is used for ovarian suppression immediately following oocyte retrieval. A delay in initiating long-acting GnRH agonist after oocyte retrieval in patients at high risk for developing OHSS should be considered.

Topics: Adolescent; Adult; Female; Fertility Agents, Female; Fertility Preservation; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Neoplasms; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

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

Triptorelin 0.2 mg and leuprolide 1 mg subcutaneous injections for triggering final follicular maturation were compared in patients with a high risk for ovarian hyperstimulation syndrome (OHSS). Infertile patients treated with GnRH antagonist protocol between January 2014 and March 2016 were recruited. Patients with high serum oestradiol levels on HCG day (>3000 pg/ml) indicating a risk of OHSS consisted of the study groups (A and B). Patients with serum oestradiol levels less than 3000 pg/ml consisted of the control group (C). A single injection of 0.2 mg triptorelin, 1 mg leuprolide and 10000 IU HCG were administered for final oocyte triggering in groups A (n = 63), B (n = 74) and C (n = 131), respectively. Demographic parameters were comparable between the groups. No cases of severe or moderate OHSS occurred in any group. The clinical pregnancy rates were 31.7%, 37.8% and 32.8% in groups A, B and C, respectively. Both injections had comparable efficacy in clinical outcome and OHSS risk. Regardless of preferred drug, GnRH agonist trigger for final oocyte maturation seems to be safe for patients with high OHSS risk, and can be safely used in fresh embryo transfer cycles.

Topics: Adolescent; Adult; Estradiol; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Infertility, Male; Leuprolide; Male; Oocytes; Oogenesis; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Risk; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate; Young Adult

Ovarian hyperstimulation syndrome is a potentially life-threatening, but preventable iatrogenic complication of in vitro fertilisation treatment. In recent years, new strategies have been developed to minimise the risk of ovarian hyperstimulation syndrome after in vitro fertilisation, including better at-risk patient identification prior to starting treatment, the use of a lower human chorionic gonadotrophin dose or alternative medication instead of human chorionic gonadotrophin to induce final oocyte maturation such as gonadotrophin-releasing hormone agonist and kisspeptin in antagonist cycles, cryopreservation of all embryos and delayed embryo transfer, and the use of oral dopamine agonists after oocyte retrieval. In this article, the advantages and limitations of those new developments are discussed and future directions towards establishment of an ovarian hyperstimulation syndrome-free in vitro fertilisation clinic are explored.

Topics: Cabergoline; Chorionic Gonadotropin; Dopamine Agonists; Ergolines; Estradiol; Estrogens; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Leuprolide; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Reproductive Control Agents; Risk Assessment

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

Ovarian hyperstimulation syndrome (OHSS) is a life- threatening complication of controlled ovarian stimulation. One of the main symptoms of OHSS is ascites. Treatment is symptomatic with resolution of the symptoms over days to weeks. We report a case of severe OHSS with persistent ascites 18 months after the diagnosis. Persistent ascites secondary to OHSS was diagnosed and single dose leuprolide acetate depot 11.25 mg was administered. At follow-up, no ascites was observed.

Topics: Adult; Ascites; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Treatment Outcome

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

To analyse the data from all controlled ovarian hyperstimulation antagonist cycles that used an agonist trigger and a freeze-all strategy to quantify the risk of ovarian hyperstimulation syndrome (OHSS) and subsequent pregnancy rates.. A retrospective study of all women attending fertility clinics at IVF Australia, Sydney, undergoing controlled ovarian hyperstimulation (COH) using an antagonist protocol that had a subsequent gonadotropin-releasing hormone (GnRH) agonist trigger and freezing of all oocytes or embryos. The primary outcome measure was to determine the rate of OHSS. The secondary outcome measure was the clinical pregnancy rate.. We collected data for 123 women. 25.2% were undergoing oocyte freezing and 74.8% underwent embryo freezing. There were no cases of OHSS, either early or late onset. The pregnancy rate was 31.7% after the first frozen cycle transfer with a cumulative pregnancy rate of 50% after two frozen embryo transfers.. Our results support the hypothesis that a GnRH agonist trigger and a freeze-all approach prevents OHSS with a good pregnancy rate.

Topics: Adult; Cryopreservation; Embryo, Mammalian; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nafarelin; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies

The use of cabergoline and coasting are both effective in reducing the risk of ovarian hyperstimulation syndrome (OHSS). Our aim was to compare the effectiveness of cabergoline with coasting to prevent moderate-severe OHSS.. Fifty-seven consecutive infertile patients (81 cycles) at risk of developing OHSS were enrolled through our computerized IVF database system. Inclusion criteria were: (i) E2 level on the day of human chorionic gonadotrophin (hCG) greater than 3,500 pg/ml; (ii) patients who underwent luteal long GnRH agonist cycle; (iii) patients who used cabergoline for OHSS prevention; (iv) patients who underwent coasting for OHSS prevention. The cabergoline group constituted 17 patients (26 cycles) who started using 0.5 mg oral cabergoline daily for 8 days on the day of hCG, whereas the coasting group constituted 40 patients (55 cycles) who underwent coasting.. Both groups were comparable regarding the women's mean age, body mass index and duration of infertility. Implantation rate, clinical pregnancy per embryo transfer and miscarriage rates were not different between the two groups. There was no OHSS in the cabergoline group (0 %), whereas there were two OHSS (3.6 %) in the coasting group; however, this difference was not significant.. In conclusion, 0.5 mg daily use of cabergoline for 8 days beginning from hCG administration is a very effective way to reduce moderate-severe OHSS without sacrificing pregnancy rates in patients at risk of developing OHSS.

Topics: Adult; Cabergoline; Dopamine Agonists; Ergolines; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Hormones; Humans; Infertility, Female; Leuprolide; Longitudinal Studies; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Young Adult

Bioactive gonadotropin-secreting pituitary adenomas are very rare in fertile women and can cause an ovarian hyperstimulation syndrome (OHSS). A 31-year-old woman with oligo-amenorrhea, severe ovarian cystic swelling and high serum estradiol was submitted to the resection of ovarian cysts and then treated with long-acting leuprolide 11.25 mg. Two months later, the ovarian multicystic hyperplasia relapsed, thus a pituitary MRI was performed and a pituitary macroadenoma was detected. In January 2010, she was referred to our Endocrinology Department where her hormonal evaluation showed high serum estradiol, FSH, α-subunit and inhibin with low LH. In April 2010, she underwent a trans-sphenoidal pituitary adenomectomy, which rapidly regularized the hormonal profile, the ovary and pituitary morphology and the menses. The case presented confirms that gonadotrophinomas occurring in reproductive-aged women frequently produce symptoms of ovarian hyperstimulation and proves that the use of GnRH analogs is not indicated in this condition.

Topics: Adenoma; Adult; Age Factors; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Humans; Leuprolide; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Pituitary Neoplasms; Recurrence; Reproduction; Treatment Failure

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with gonadotropins followed by the administration of human chorionic gonadotropin (hCG) to trigger the final steps of oocyte maturation. Gonadotropin-releasing hormone (GnRH) analogs are thought to be effective in preventing this complication and a clinical trial has found a lower incidence of OHSS in patients treated with these molecules. Our aim was to analyze the in vivo effect of a GnRH-I agonist on corpus luteum development and regression, ANGPT-1, ANGPT-2 and Tie-2 protein expression and luteal blood vessel stabilization, the expression of the steroidogenic acute regulatory protein (StAR) and the cytochrome P450 side-chain cleavage enzyme (P450scc) and cell proliferation, in ovaries from an OHSS rat model. To this end immature female Sprague-Dawley rats were hyperstimulated and treated with a GnRH-I agonist from the start of pregnant mare serum gonadotropin (PMSG) administration until the day of hCG injection for 5 consecutive days. Blood and tissue samples were collected 48h after hCG injection. Vascular endothelial growth factor VEGF levels were evaluated in the peritoneal fluid by ELISA. Serum progesterone and estradiol were measured by RIA. Histological features of sectioned ovaries were assessed in hematoxylin and eosin (H&E) stained slides. Luteal blood vessel stability, cell proliferation and apoptosis were assessed by immunohistochemistry for SMCA, PCNA, and TUNEL, respectively. P450scc, StAR, FLK-1, ANGPT-1, ANGPT-2, Tie-2 and PCNA protein levels were evaluated by Western blot from dissected corpora lutea (CL). The treatment with the GnRH-I agonist significantly decreased serum progesterone and estradiol levels as well as P450scc and StAR protein expression in the untreated OHSS group. In addition, the agonist significantly decreased the number of CL in the OHSS group, as compared with the untreated OHSS group. In the OHSS group, the area of periendothelial cells in the CL was larger than that of the control group. However, the treatment with the GnRH-I agonist significantly reduced the area of periendothelial cells in the CL in the OHSS group. The luteal levels of ANGPT-1 and its receptor Tie-2 significantly increased in the OHSS group when compared with the control group. Conversely, the administration of the GnRH-I agonist significantly decreased the levels of these factors in the CL from the OHSS group, as compared with the untreated OHSS group. In additio

Topics: Angiopoietin-1; Angiopoietin-2; Animals; Apoptosis; Blood Vessels; Cell Proliferation; Cholesterol Side-Chain Cleavage Enzyme; Corpus Luteum; Female; Fertility Agents, Female; Gonadal Steroid Hormones; Gonadotropins, Equine; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovary; Phosphoproteins; Rats; Rats, Sprague-Dawley; Receptor, TIE-2; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

This retrospective study of fresh autologous blastocyst transfers in high responders compared ongoing pregnancy rates in cycles that followed trigger with GnRH agonist (GnRHa) alone with standard luteal support, GnRHa alone with enhanced luteal support, or GnRHa with concomitant low-dose hCG (dual trigger). Ongoing pregnancy rates were significantly increased with the dual trigger or with enhanced luteal support, whereas the incidence of clinically significant ovarian hyperstimulation syndrome was 0.0% in the groups receiving only GnRHa and 0.5% (1 of 182) in patients receiving GnRHa with concomitant low-dose hCG.

Topics: Adult; Chi-Square Distribution; Chorionic Gonadotropin; Drug Therapy, Combination; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nevada; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Topics: Adult; Drug Administration Schedule; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Oocytes; Oogenesis; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Risk Factors; Treatment Outcome; Withholding Treatment

The aim of this study in patients at risk of ovarian hyperstimulation syndrome (OHSS) was to determine the efficacy and safety of luteal support using human chorionic gonadotrophin (HCG) after triggering ovulation with gonadotrophin-releasing hormone (GnRH) agonist in IVF/intracytoplasmic sperm injection antagonist cycles. A total of 192 OHSS-risk patients, following a GnRH antagonist protocol (0.25mg/day cetrorelix) during recombinant FSH stimulation, were triggered with 1.5mg s.c. leuproreline for ovulation. A total of three boluses of HCG were used for luteal support, 1000IU (group A, n=44), 500IU (group B, n=115) or 250IU (group C, n=33) every third day, starting the day after oocyte retrieval. For the reproductive outcome, main variables were biochemical and clinical pregnancy rates, and for OHSS, the variables were the numbers of moderate and severe OHSS cases. Overall pregnancy rate was 51.8% and clinical pregnancy rate was 43.4%. This study observed eight cases of moderate (4.2%) and seven of severe OHSS (3.6%). Six out of the seven (85.7%) severe cases were late-onset OHSS, related to pregnancy. In conclusion, GnRH agonist single dose for triggering ovulation and low doses of HCG used as luteal-phase support seem to secure a normal pregnancy outcome without increasing the OHSS risk.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Retrospective Studies; Risk Assessment

Acceptable rates of fertilization, implantation, clinical pregnancy, ongoing pregnancy, and early pregnancy loss were achieved in high responders after triggering final oocyte maturation with a combination of leuprolide acetate and hCG (1,000 to 2,500 IU). These findings, along with the absence of ovarian hyperstimulation syndrome, suggest that this dual trigger is safe and effective for oocyte maturation in patients with significant risk factors for ovarian hyperstimulation syndrome.

Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Leuprolide; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Treatment Outcome

We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Hyperstimulated rats received excessive doses of pregnant mare serum gonadotropin (PMSG; 50 IU/d) for 4 consecutive days, from d 25 to 28 of life, followed by 25 IU human chorionic gonadotropin (hCG) on d 29. Control rats received 10 IU PMSG on d 27 of life, followed by 10 IU hCG on d 29. GnRHa (leuprolide 100 microg/kg.d) was administered to some hyperstimulated rats either on d 29 and 30 (short-term GnRHa treatment) or from d 25 to 30 (long-term GnRHa treatment). Ovarian vascular density (vessels per 10 mm(2)) and vessel endothelial area (percent) were assessed by immunohistochemical analysis of the distribution of von Willebrand factor, whereas vascular permeability was evaluated based on leakage of Evans blue. High doses of PMSG and hCG significantly increased ovarian weight, vascular permeability, vascular density, and the vessel endothelial area and significantly reduced expression of claudin-5 protein and mRNA. All of these effects were significantly and dose-dependently inhibited by administration of GnRHa. This suggests that reduced expression of claudin-5 plays a crucial role in the increased ovarian vascular permeability seen in OHSS and that its expression can be modulated by GnRHa treatment. Indeed, preventing redistribution of tight junction proteins in endothelial cells and the resultant loss of endothelial barrier architecture might be the key to protecting patients against massive extravascular fluid accumulation in cases of OHSS.

Topics: Analysis of Variance; Animals; Capillary Permeability; Chorionic Gonadotropin; Claudin-5; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Endothelial Cells; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins, Equine; Leuprolide; Membrane Proteins; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Rats; Rats, Sprague-Dawley; RNA, Messenger; Statistics, Nonparametric; Tight Junctions

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

We attempted ovarian stimulation using gonadotropins in 14 chimpanzees. Subjects were given a single administration of leuprorelin acetate, followed by repeated administration of human menopausal gonadotropin (hMG) for 16-21 days. During the dosing period, the ovarian follicle diameter and count were measured by transvaginal ultrasonography. The hormone administration induced the development of multiple follicles, and multiple oocytes were subsequently retrieved. However, the follicle count was decreased, suggesting atresia, in some subjects. Statistically, the final follicle diameter was dependent on the dosing duration and the hMG dose in the late stage, while the maximum follicle count during hMG administration was dependent on age and the hMG dose in the early stage. Five subjects showed mild ovarian hyperstimulation syndrome (OHSS)-like symptoms with a high serum estradiol (E2) concentration. These results suggest that leuprorelin acetate plus hMG administration successfully stimulates the development of multiple ovarian follicles for oocyte retrieval and that the serum E2 concentration is predictive of OHSS-like symptoms in chimpanzees.

Topics: Animals; Estradiol; Female; Follicular Atresia; Humans; Kinetics; Leuprolide; Menotropins; Monkey Diseases; Oocytes; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pan troglodytes; Progesterone; Superovulation; Ultrasonography

Using hyperstimulated rats, to elucidate the mechanisms of gonadotropin-releasing hormone agonist (GnRH-a) treatment to prevent early ovarian hyperstimulation syndrome (OHSS).. Descriptive study of hyperstimulated rats as an early OHSS model with Western blot analysis, Northern blot hybridization, and vascular permeability assay.. Experimental laboratory research.. Sprague-Dawley female rats were used for collecting ovarian samples.. Hyperstimulated rats received consecutive GnRH-a treatment from the start of pregnant mare serum gonadotropin (PMSG) treatment through 2 days after hCG administration.. Expressions of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1: Flt-1), VEGF receptor-2 (VEGFR-2: KDR/Flk-1), and vascular permeability by Evans blue leakage.. GnRH-a treatment significantly reduced expressions of VEGF, VEGFR-1, and VEGFR-2 both in mRNA and protein levels in the ovaries of hyperstimulated rats. GnRH-a treatment also reduced vascular permeability in the ovaries of hyperstimulated rats.. It is speculated that GnRH-a treatment may prevent early OHSS by reducing vascular permeability through the decrease in VEGF and its receptors.

Topics: Animals; Blotting, Northern; Blotting, Western; Capillary Permeability; Coloring Agents; Evans Blue; Female; Gonadotropin-Releasing Hormone; Hormones; Leuprolide; Organ Size; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Rats; Rats, Sprague-Dawley; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger; Vascular Endothelial Growth Factor A

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

Topics: Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Male; Metaphase; Oocytes; Ovarian Hyperstimulation Syndrome; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Treatment Outcome

To report a case of a gonadotroph adenoma diagnosed after a dramatic increase in estradiol level and ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist.. Case report.. Outpatient practice and university hospital.. A 35-year-old woman who presented with infertility, amenorrhea, and an elevated basal estradiol concentration.. Ultrasonography, laparoscopy, endocrinologic assays, magnetic resonance imaging, transsphenoidal surgery, and immunocytochemical staining.. Ultrasonography and laparoscopy demonstrated bilaterally enlarged ovaries containing multiple preovulatory follicles, similar in appearance in those women undergoing controlled ovarian hyperstimulation with exogenous FSH. The serum estradiol level was moderately elevated, the FSH level was within the normal range, and LH was suppressed. Administration of leuprolide acetate resulted in very elevated estradiol concentrations and even larger ovarian cysts. Magnetic resonance imaging demonstrated a sellar mass. Examination of the tissue excised by transsphenoidal excision of the mass showed a pituitary adenoma that stained strongly for FSH.. Regular menses resumed soon after excision of the gonadotroph adenoma, followed by a spontaneous pregnancy.. Gonadotroph adenoma should be suspected in a reproductive age woman with oligomenorrhea or amenorrhea, infertility, multiple preovulatory follicles, and a persistently elevated serum estradiol concentration. Exacerbation of the ovarian hyperstimulation in response to a gonadotropin-releasing hormone agonist in this setting also strongly suggests a gonadotroph adenoma but can be avoided by recognizing the presenting features of this condition.

Topics: Adenoma; Adult; Estradiol; Female; Fertility Agents, Female; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Pituitary Gland, Anterior; Pituitary Neoplasms; Pregnancy

To report a case of bilateral massive vulvar edema following lower abdominal paracentesis in a patient with ovarian hyperstimulation syndrome.. Case report.. University teaching hospital.. A 32-year-old woman with primary infertility.. The patient underwent ovarian stimulation with leuprolide acetate, highly purified FSH, and hCG. Because of the development of severe ovarian hyperstimulation syndrome, bilateral paracentesis through the lower abdominal quadrants was performed.. Treatment of ovarian hyperstimulation syndrome.. Development of bilateral massive vulvar edema 24 hours after lower abdominal paracentesis.. This case report suggests that lower abdominal paracentesis could be the cause of vulvar edema development in ovarian hyperstimulation syndrome, probably due to a fistulous tract created between the peritoneal cavity and the subcutaneous tissues.

Topics: Adult; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Edema; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Paracentesis; Vulvar Diseases

Exogenous administration of gonadotropin-releasing hormone agonist (GnRHa) induces an endogenous midcycle gonadotropin surge. However, its use to induce ovulation and maintain luteal function in non-in vitro fertilization patients who receive ovarian stimulation is unknown.. Five infertile women who underwent controlled ovarian hyperstimulation with human menotropin developed multiple ovarian follicles. In an attempt to circumvent the potential ovarian hyperstimulation syndrome, 1 mg of leuprolide acetate was administered subcutaneously to three patients in an attempt to induce the endogenous luteinizing hormone surge. All three patients began menstruation six to seven days after GnRHa administration with serum progesterone levels between 0.2 and 0.5 ng/mL. Similar ovarian stimulation cycles with ovulation induced by human chorionic gonadotropin in these individuals revealed a normal luteal phase length and midluteal progesterone levels. When double doses of leuprolide acetate were used on two patients, normal luteal length and midluteal serum progesterone levels occurred.. A single bolus of GnRHa during the late follicular phase may be inadequate to initiate normal luteal function in cycles with ovarian hyperstimulation.

Topics: Adult; Female; Fertility Agents, Female; Humans; Infertility, Female; Injections, Subcutaneous; Leuprolide; Menstrual Cycle; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Progesterone

To study the effect of postponing hCG administration while continuing daily GnRH agonist therapy ("coasting") on highly responsive patients undergoing IVF-ET.. Retrospective analysis.. University-affiliated Center for Fertility and Reproductive Medicine.. Patients undergoing IVF-ET from March 1995 to March 1997.. Three groups of IVF-ET patients were compared to explore the effect of coasting on cycle outcome: a group of highly responsive coasted patients, a group of equally responsive noncoasted patients, and an age-matched normally responsive control group. Two groups of coasted patients were also compared to assess the effect of E2 levels at the time that they met the follicular criteria for hCG administration. Last, the effect of varying coast duration was examined by regression analysis.. Patient characteristics, outcome parameters, and incidence of ovarian hyperstimulation syndrome (OHSS).. Coasting had no detrimental effect on cycle outcome in the subset studied. Regression analysis, however, suggests an inverse relationship between coast duration and the number of mature oocytes retrieved as well as the clinical pregnancy rate.. Coasting in the studied subset of IVF patients did not adversely affect cycle outcome parameters or the incidence of OHSS, but prolonged coasting intervals may impair IVF cycle outcome.

Topics: Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Infertility; Leuprolide; Logistic Models; Male; Microinjections; Ovarian Hyperstimulation Syndrome; Pregnancy; Progesterone; Retrospective Studies

Our purpose was to examine the rate of immature oocyte recovery and their potential for in vitro maturation from canceled human menopausal gonadotropin cycles due to the risk of having ovarian hyperstimulation syndrome develop.. Patients underwent ultrasound-guided immature oocyte pickup. The number of oocytes recovered from these patients was recorded, and then cultured in vitro. Cumulus expansion and the stage of nuclear maturation were observed after 24 and 48 hr, respectively.. Seventeen patients underwent 20 immature oocyte recoveries. A total of 162 oocytes (8.1 oocytes/patient) was obtained. All of the oocytes were enclosed in dense layers of cumulus cells. Among them, 78.4% showed cumulus expansion after 24 hr and 66% completed meiotic maturation to metaphase II after 48 hr in culture. There was only one immature oocyte pickup in which no oocytes were recovered (95% recovery rate). None of the patients had ovarian hyperstimulation syndrome develop.. Immature oocytes can be recovered from canceled human menopausal gonadotropin cycles in patients who are at potential risk for severe hyperstimulation syndrome. These oocytes can be matured in vitro and can be used for clinical and research purposes as well.

Topics: Antineoplastic Agents, Hormonal; Buserelin; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Granulosa Cells; Humans; Infertility, Female; Infertility, Male; Leuprolide; Male; Menstrual Cycle; Oocytes; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Risk Factors

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.

Topics: Adult; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation following the sole administration of gonadotrophin-releasing hormone agonists (GnRHa) is exceedingly rare. We hereby report on two infertile patients undergoing in-vitro fertilization-embryo transfer who developed ovarian hyperstimulation under such circumstances. In both patients, GnRHa were administered using the 'long protocol' regimen. The first patient developed ovarian hyperstimulation on two occasions, with mid-luteal depot administration of triptorelin and with early follicular triptorelin, administered as daily subcutaneous injections. In both cycles, within 2 weeks of triptorelin therapy, massive ovarian multifollicular enlargement occurred, concomitant with high serum oestradiol concentrations, which resolved spontaneously following expectant management. The second patient developed ovarian hyperstimulation following daily injections of leuprolide acetate starting at the mid-luteal phase. The final stage of ovulation was triggered by human chorionic gonadotrophin (HCG) and 11 oocytes were retrieved. In-vitro fertilization resulted in embryo formation, but failed to result in pregnancy. The same phenomenon recurred in a subsequent cycle despite preventive pretreatment with an oral contraceptive. A negative GnRH test, performed just before HCG administration, suggested than an ongoing 'flare-up effect' was unlikely to cause ovarian stimulation. Ovarian hyperstimulation can occur following the sole administration of GnRHa irrespective of the preparation used and the administration protocol. Although spontaneous resolution is the rule, once this condition has developed, HCG administration and oocyte retrieval are feasible. This rare entity probably represents an exaggerated form of ovarian cyst formation following GnRHa administration, the underlying pathophysiology of which remains unresolved.

Topics: Administration, Cutaneous; Adult; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Leuprolide; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Time Factors; Triptorelin Pamoate

To assess the efficacy of a novel protocol-microdose GnRH agonist (GnRH-a), FSH, and GH, for the stimulation of IVF patients who were canceled previously on a standard luteal GnRH-a, FSH, GH protocol.. Prospective evaluation using the patient's previous IVF stimulation attempt as historic controls.. Private practice assisted reproductive technology center.. Thirty-two patients who had prior ovulation induction cycles canceled using luteal phase GnRH-a suppression followed by exogenous gonadotropins and GH.. Precycle treatment with oral contraceptives followed by follicular phase administration of 40 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and FSH supplemented with GH beginning on cycle day 5.. Paired analysis of E2 day 5, number of follicles, ampules of FSH required, and cancellation rate. The number of oocytes, embryos, embryo quality, implantation rate, and pregnancy rate (PR) were determined for completed cycles on the microdose GnRH-a, FSH, GH protocol.. Controlled ovarian hyperstimulation was superior during microdose GnRH-a, FSH, GH stimulation when compared with the prior luteal GnRH-a cycle. Specifically, there was a higher E2 response, more oocytes, fewer cycle cancellations, and no premature LH surge or luteinization. The microdose GnRH-a, FSH, GH protocol produced an average of 10 oocytes and a 50% ongoing PR.. The microdose GnRH-a, FSH, GH protocol is superior to standard protocols for the treatment of patients with decreased ovarian reserve undergoing controlled ovarian hyperstimulation for IVF.

Topics: Adult; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Growth Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies

The study presented herein evaluated whether 26 of 122 consecutive women who tend to hyper-respond (serum estradiol >4,000 pg/ml or >30 follicles) following controlled ovarian hyperstimulation for in vitro fertilization have higher serum FSH levels at certain critical stages during the follicular phase. Baseline day-2 serum FSH and blood levels taken on days 5 and 6 of human menopausal gonadotropin therapy were not different in the hyper-responders from those responding normally. The only significant difference in serum FSH was seen on the day of human chorionic gonadotropin where it was actually lower in the hyper-responders. Thus, there does not appear to be a critical serum FSH level which would dictate a decrease in gonadotropins to prevent hyper-response.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Risk Factors; Ultrasonography

In-vitro fertilization patients (n = 15) at risk of ovarian hyperstimulation syndrome (OHSS) (oestradiol > or =4500 pg/ml on the day of human chorionic gonadotrophin administration and 25 or more follicles of intermediate or large size) underwent aspiration of all follicles and cryopreservation of all fertilized oocytes at the pronuclear stage. Patients were monitored for up to 2 weeks post-retrieval. Subsequent transfer of cryopreserved-thawed embryos was performed in programmed cycles using exogenous oestrogen and progesterone for endometrial preparation. Two patients (13%) developed OHSS necessitating hospitalization and vaginal aspiration of ascitic fluid. Two other patients (13%) developed moderate OHSS requiring ascitic fluid vaginal aspiration in the office setting, with dramatic improvement of the condition. Subsequent transfer of cryopreserved-thawed embryos yielded a clinical pregnancy rate of 58% per transfer and ongoing or delivery rates of 42 and 67% per transfer and per patient respectively. By eliminating pregnancy potential with cryopreservation of all prezygotes and examining the pregnancy potential with subsequent cryopreserved-thawed transfers, it is concluded that OHSS is reduced, but not eliminated for patients at risk. Subsequent transfer of cryopreserved-thawed prezygotes in a programmed cycle with exogenous steroids yields an excellent pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Cryopreservation; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Hot Temperature; Humans; Infertility, Female; Leuprolide; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Risk Factors

The purpose of this study was to evaluate the applicability of continuing daily injectable GnRHa, after pituitary desensitization, for the first 4 or 5 days of ovarian stimulation. We proposed a new calculation and estimated that it took as early as 6 to 7 days for pituitary and gonadotropin release to return after cessation of daily administered leuprolide acetate. A modified regimen based on this new calculation, i.e. Daily administered GnRHa continued for the first 4 or 5 days with ovarian stimulation after pituitary desensitization had been achieved was applied to patients undergoing assisted reproductive technology (ART). Thirty-five patients prospectively assigned to use this early discontinuation regimen were analyzed with respect to age, indications, duration of ovarian stimulation, dose of exogenous gonadotropin required, ovarian response and oocytes obtained, rate of fertilization, and rates of pregnancy. There was no spontaneous LH surge occurred. Premature luteinization occurred in one patient. We concluded that, after pituitary desensitization, there was no spontaneous LH surge when daily administered GnRHa continued for 4 or 5 days only with ovarian stimulation. Impacts on the ART outcome required further evaluation in a prospectively randomized study. Based on theoretical estimation, cessation of GnRHa at the beginning of ovarian stimulation might eliminate most, but not all, spontaneous LH surges.

Topics: Adult; Female; Follicle Stimulating Hormone; Humans; Leuprolide; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Pregnancy; Prospective Studies

A recently identified cytokine, vascular endothelial growth factor (VEGF, vascular permeability factor) has been implicated in ovarian hyperstimulation syndrome in women undergoing assisted reproduction. We postulate that circulating and urinary VEGF values increase following gonadotrophin stimulation, in parallel with the increased ovarian vascularity. A VEGF radioimmunoassay was developed using iodinated VEGF as tracer, a goat anti-VEGF serum as antiserum and recombinant human VEGF as standard. The specificity of the assay was confirmed by comparing the reverse phase high-performance liquid chromatography (HPLC) pattern of VEGF immunoactivity in urine and urine spiked with recombinant VEGF. Urine was concentrated 5-fold prior to measurement by the radioimmunoassay. VEGF:creatinine ratios in early morning urine samples were used to monitor daily urinary VEGF concentrations based on its high correlation (r = 0.77, P < 0.001) with VEGF concentrations in 24 h urine collections. No diurnal variation in VEGF:creatinine ratios was detected. VEGF:creatinine ratios were determined daily from nine women undergoing gonadotrophin-releasing hormone (GnRH) agonist/gonadotrophin treatment. In a further 16 women, early morning urine samples were collected in the peri-ovulatory period. A significant increase (P < 0.005, n = 25) was observed in VEGF:creatinine ratios following human chorionic gonadotrophin (HCG) administration. VEGF:creatinine ratios correlated poorly (r < 0.34) with plasma oestradiol, follicle number and size. It is concluded that urinary VEGF/creatinine ratios increase following HCG stimulation.

Topics: Chorionic Gonadotropin; Chromatography, High Pressure Liquid; Circadian Rhythm; Endothelial Growth Factors; Female; Fertilization in Vitro; Humans; Leuprolide; Lymphokines; Menotropins; Ovarian Hyperstimulation Syndrome; Pregnancy; Radioimmunoassay; Recombinant Proteins; Sensitivity and Specificity; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Severe ovarian hyperstimulation syndrome occurred after the administration of LA to suppress multicystic ovaries. It is possible that this patient with multiple ovarian cysts, each 2 to 3 cm in size, is at increased risk for a paradoxical stimulatory rather than inhibitory response to GnRH-a.

Topics: Adult; Estradiol; Female; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Testolactone

To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET).. Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed.. None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally.. This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Time Factors

To determine if cultured human granulosa cells (GCs) obtained from women at risk for ovarian hyperstimulation syndrome (OHSS) possess altered steroidogenic capacity.. Prospective analysis of 28 consecutive in vitro fertilization-gamete intrafallopian transfer (IVF-GIFT) cycles.. In Vitro Fertilization Program at Rush Presbyterian St. Luke's Medical Center in Chicago, Illinois.. Eighteen patients (group I) with serum estradiol (E2) levels > 7,342 pmol/L on the day of exogenous human chorionic gonadotropin (hCG) administration (day 0) with > 10 ovarian follicles present (high risk for OHSS); 10 patients (group II) with E2 < or = 7,342 pmol/L on day 0 and < or = 10 follicles.. Human GCs obtained during gonadotropin-releasing hormone agonist-pretreated IVF-GIFT cycles were cultured in the absence (control) or presence (hCG) of hCG, 1 IU/mL, and/or androstenedione (A) 10(-7) M. Granulosa cells obtained from follicles < or = 15 mm diameter were cultured separately from those obtained from follicles > 15 mm diameter.. Estradiol (E2) and progesterone were measured in tissue-culture medium by a solid-phase direct radioimmunoassay.. In vitro E2 production by cultured GCs was significantly increased in follicles < or = 15 mm diameter from women considered at risk of developing OHSS (group I). Estradiol response to hCG and/or A appeared enhanced in all follicles in group I. Progesterone production in the basal and hCG challenged state was greater in cells obtained from large follicles in group I than in group II.. Ovarian hyperstimulation syndrome appears to be a function of an increased number of follicles that express an enhanced steroidogenic capacity.

Topics: Cells, Cultured; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Gamete Intrafallopian Transfer; Granulosa Cells; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Progesterone; Prospective Studies; Risk Factors

Topics: Adult; Delayed-Action Preparations; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Triptorelin Pamoate

Initial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-a/human menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E2) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E2 secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-a/hMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chorionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E2 was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6-8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E2 was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Gamete Intrafallopian Transfer; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Menotropins; Ovarian Hyperstimulation Syndrome; Pituitary Gland