leuprolide and Infertility

To determine the outcome of spontaneous conceptions in women who received GnRH agonists during mid-luteal phase down-regulation before IVF treatment.. Retrospective analysis of case records and study of the literature.. Two university-affiliated reproductive medicine units.. Seventy-three women who conceived spontaneously after starting down-regulation with a GnRH agonist before controlled ovarian hyperstimulation.. None.. Course and clinical outcome of pregnancies.. Seventy-four pregnancies occurred in 73 women who received a GnRH agonist. Of these patients, 6 (8%) had a biochemical pregnancy, 6 (8%) had an ectopic pregnancy, 21 (28%) miscarried, and 41 pregnancies resulted in successfully delivered babies; there were 2 cases of congenital abnormalities.. These cases, together with other published data, suggest that pregnancy outcome is not adversely affected by exposure to GnRH agonist during luteal-phase down-regulation. A central register of pregnant women who received a GnRH agonist is needed.. The aim was to determine the outcome of spontaneous conceptions in women who received gonadotropin-releasing hormone agonists (GnRH-a) during mid-luteal phase down-regulation before in vitro fertilization treatment. The authors reviewed available literature and retrospectively studied 73 patients from two infertility centers in Melbourne, Australia, who became pregnant after they began to take GnRH-a before controlled ovarian hyperstimulation. The main outcome measures were the course and clinical outcome of pregnancies. 74 pregnancies occurred in 73 women who received GnRH-a. Of these patients, 6 (8%) had a biochemical pregnancy, 6 (8%) had an ectopic pregnancy, 21 (28%) had a miscarriage, and 41 pregnancies resulted in successfully delivered babies, with 2 cases of congenital abnormalities. These cases, together with other published data, indicate that pregnancy outcome is not adversely affected by exposure to GnRH-a during luteal phase down-regulation. A central register of pregnant women who received GnRH-a is needed.

Topics: Buserelin; Down-Regulation; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Leuprolide; Male; Nafarelin; Outcome Assessment, Health Care; Pregnancy; Retrospective Studies

To compare the level of apoptosis and DNA fragmentation in the human granulosa cell (GC) layer exposed to an agonist or antagonist of GnRH in intracytoplasmic sperm injection (ICSI) cycles supplemented with recombinant LH (rLH).. Patients without ovulatory dysfunction, aged ≤37 years and in their first ICSI cycle were prospectively randomised to receive either a long GnRH agonist protocol or a multi-dose antagonist protocol. In both groups, recombinant FSH supplemented with rLH was used for ovarian stimulation, and the GCs were collected during oocyte denudation. The GCs were then analysed for DNA fragmentation by TUNEL assay and for apoptosis using the annexin-V assay. The outcomes were given as the percentage of GCs with DNA fragmentation and apoptosis out of the total number of GCs analysed. Comparison of the agonist versus the antagonist group was performed using the Mann-Whitney test.. DNA fragmentation: 32 patients were included in either the GnRH agonist group (n=16) or the antagonist group (n=16). The percentage of GCs with positive DNA fragmentation did not differ significantly (P=0.76) between the agonist group (15.5 ± 9.4%) and the antagonist group (18.8 ± 13.3%). Apoptosis: 28 patients were included in either the GnRH agonist group (n=14) or the antagonist group (n=14). The percentage of GCs positive for apoptosis did not differ significantly (P=0.78) between the agonist group (34.6 ± 14.7%) and the antagonist group (36.5 ± 22%).. The results suggest that therapy with either an agonist or antagonist of GnRH is associated with comparable levels of DNA fragmentation and apoptosis in granulosa cells in ICSI cycles supplemented with rLH.

Topics: Adult; Apoptosis; Cell Separation; DNA Fragmentation; Family Characteristics; Female; Gonadotropin-Releasing Hormone; Granulosa Cells; Hormone Antagonists; Humans; Infertility; Leuprolide; Luteinizing Hormone; Male; Oocyte Retrieval; Ovulation Induction; Recombinant Proteins; Sperm Injections, Intracytoplasmic

Despite the probable inhibitory effects of GnRH analogues on ovarian steroidogenesis in vitro, their association with assisted reproduction protocols shows favorable results. This suggests that there are important differences in the behaviors of these drugs when administered in vivo versus in vitro. To clarify these differences, this study was designed to analyze the effect of leuprolide acetate (LA) on ovarian steroidogenesis in women undergoing In Vitro Fertilization (IVF). A prospective, randomized open label study was conducted on 14 women (26-35 years): seven receiving only gonadotrophins (Group 1) and seven receiving gonadotrophin plus LA at 1mg/day (Group 2). The LA in vivo effect was determined with serum and follicular fluid (FF) samples and via luteinized granulosa cell cultivation (GCC), where cells were obtained during oocyte retrieval after ovarian hyperstimulation. In vitro analysis was performed via addition of LA to GCC only for Group 1 (without LA) at progressively higher concentrations (0, 10(-12), 10(-9) and 10(-6)M). In vivo, the main observation was a reduction in androgen production in Group 2, represented by lower androstenedione production in FF (G1=6479+/-3458; G2=3021+/-1119 ng/ml; p=0.04) and a lower testosterone peak in GC at 96h (G1=0.64+/-0.12 ng/ml; G2=0.50+/-0.19 ng/ml; P=0.02), but a higher fertilization rate (G1=67%; G2=83%; p=0.009). In vitro, testosterone, estradiol and progesterone were also reduced by LA, even though this reduction occurred for progesterone only at the highest LA dosage (10(-6)M; 606.0+/-114.3 ng/ml versus 1524.0+/-246.5 ng/ml; p=0.02). Results show that LA reduces ovarian steroidogenesis in vivo by essentially inhibiting androgen synthesis; whereas, in vitro, ovarian steroidogenesis is reduced overall.

Topics: Adult; Cells, Cultured; Drug Combinations; Female; Fertility Agents, Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Gonadotropins; Granulosa Cells; Humans; In Vitro Techniques; Infertility; Leuprolide; Ovary; Prospective Studies; Steroids

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

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E2) levels (p < 0.001 and p < 0.05, respectively), FF E2 and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E2 levels.

Topics: Adult; Androstenedione; Chorionic Gonadotropin; Estradiol; Female; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Infertility; Insulin-Like Growth Factor I; Leuprolide; Luteinizing Hormone; Ovulation Induction; Pregnancy; Vascular Endothelial Growth Factor A

Recent success in polychemotherapy (PCT) in adolescent female cancer patients has become a source of concern for specialists who also strive to preserve fertility. We studied whether gonadotropin-releasing hormone (GnRH) analogs could prevent the early onset of ovarian insufficiency postchemotherapy and protect fertility.. The patients were divided into three groups: Control group 1 (Group A), premenarchal patients aged 3 to 7.5 years (n = 5), were not given GnRH analogs administered prior to PCT. Postmenarchal patients (Group B), aged 14.7 to 20 years (n = 12) with normal menstrual rhythm and ovulatory cycles, received treatment with GnRH analogs prior to PCT. Control group 2 (Group C), postmenarchal patients aged 15.9 to 20 years (n = 4), received PCT but no GnRH analog protection. All groups received the PCT regimens CAVPE, CVPP, ABVD, TAMO, ARA-C, and MTT. In group B, leuprolide acetate inhibition was obtained with a depot injection administered each month before and during treatment with PCT. To accelerate the timing of ovarian regression, a subcutaneous injection (0.2 mg) was administered simultaneously.. In Group A, patients had spontaneous menarche between the ages of 12 and 17.9 years, followed by normal menstruation and ovulatory cycles. Three patients became pregnant. After GnRH analog withdrawal, Group B patients continued with normal ovulatory cycles. Two patients became pregnant. Group C patients presented hypergonadotrophic hypoestrogenic amenorrhea.. GnRH analog treatment before and during PCT enhances ovarian function and preserves adolescent fertility. The results must be confirmed in a larger study.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Drug Administration Schedule; Female; Fertility; Fertility Agents, Female; Hodgkin Disease; Humans; Infertility; Leuprolide; Lymphoma, Non-Hodgkin; Menstrual Cycle; Ovary; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pregnancy; Thymoma

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2,500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Leuprolide; Luteal Phase; Luteinizing Hormone; Male; Menotropins; Pregnancy; Pregnancy Rate; Sperm Count; Sperm Motility

A total of 100 women undergoing ovarian stimulation with gonadotrophin-releasing hormone agonist (GnRHa) and a human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF) participated in this randomized comparative study. Leuprolide acetate at a dose of 0.5 mg/day s.c. (n = 52, group I), or low-dose leuprolide acetate depot at a dose of 1.88 mg s.c. (n = 48, group II), was started on days 21-23 of the cycle. Stimulation with 225 IU/day HMG was started after pituitary desensitization had been achieved. The luteal phase was supported by human chorionic gonadotrophin (HCG) i.m. injection. There were no statistical differences in baseline oestradiol (24.5 +/- 4.8 versus 21.9 +/- 4.5 pg/ml) and follicle stimulating hormone (FSH) concentrations (3.9 +/- 1.9 versus 3.2 +/- 1.8 mIU/ml), and concentrations on the day of HCG administration of oestradiol (1657 +/- 245 versus 1512 +/- 165 pg/ml), luteinizing hormone (LH; 6.2 +/- 4.8 versus 5.6 +/- 4.3 mIU/ml) and FSH (10.6 +/- 2.8 versus 10.8 +/- 3.6 mIU/ml). There were also no statistical differences in the HMG dosage (26.8 +/- 1.8 versus 28.5 +/- 1.5), the number of oocytes retrieved (7.6 +/- 3.0 versus 8.1 +/- 4.3), the number of oocytes fertilized (5.3 +/- 2.1 versus 5.6 +/- 3.0) and the number of embryos transferred (3.5 +/- 1.3 versus 3.4 +/- 1.6). There was no evidence of a premature LH surge in either group, but two patients appeared to have a poor response in the leuprolide acetate group (group I). There were 11 pregnancies (21.2%) after the use of leuprolide acetate and 12 pregnancies (25.0%) in those given leuprolide acetate depot; no statistical difference existed between these two groups. Thus, a s.c. low-dose leuprolide acetate depot injection may offer a useful alternative for pituitary suppression in ovarian stimulation for IVF.

Topics: Adult; Chorionic Gonadotropin; Clinical Protocols; Delayed-Action Preparations; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Injections, Subcutaneous; Leuprolide; Menotropins; Ovulation Induction; Pituitary Gland; Pregnancy

In gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin.. Progesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P < 0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P < 0.05) and ongoing/delivered pregnancy (P < 0.02) for both the day of and the day after human chorionic gonadotropin.. The study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Humans; Infertility; Injections, Intramuscular; Leuprolide; Male; Menotropins; Oocytes; Predictive Value of Tests; Pregnancy; Progesterone; Radioimmunoassay; Regression Analysis; Reproductive Techniques; Retrospective Studies

To compare two gonadotropin-releasing hormone agonists (GnRH-a), buserelin acetate and leuprolide acetate [LA], used in combination with gonadotropins in ovarian stimulation for in vitro fertilization (IVF).. Randomized prospective study.. Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona.. Thirty-five pairs of IVF patients who were matched on age, indication, and number of attempts. These women were randomized to receive either buserelin acetate plus gonadotropins (group B) or LA plus gonadotropins (group L).. Luteolysis, ovarian response, and IVF outcome.. The mean time for total ovarian arrest and the total dose of gonadotropins and estradiol levels on the day of human chorionic gonadotropin administration were similar in the two groups of patients. The number of follicles punctured, the number of oocytes retrieved, and the percentage of mature oocytes in group L were significantly higher. The number of embryos suitable for replacement and cryopreservation was higher in group L compared with group B approaching statistical significance.. Our results warrant further studies to compare different GnRH-a as therapeutic tools in IVF.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Corpus Luteum; Cryopreservation; Embryo, Mammalian; Estradiol; Female; Fertilization in Vitro; Humans; Infertility; Leuprolide; Oocytes; Pregnancy; Prospective Studies; Random Allocation

The clinical outcomes of five groups of infertility patients receiving frozen-thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone (GnRH) agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups: tubal infertility, polycystic ovary syndrome (PCOS), endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention: group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B (control group) was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively (P<0.05). The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%,respectively (P<0.05). The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist cotreatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Topics: Adult; Cryopreservation; Embryo Culture Techniques; Embryo Transfer; Estrogens; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Leuprolide; Male; Pregnancy; Pregnancy Outcome; Pregnancy, Ectopic; Progesterone

Autoimmune estrogen dermatitis is a cyclical cutaneous eruption that occurs premenstrually and goes to the rapid resolution within a few days of menstrual cycles. The disorder has variable clinical manifestations consisting of macules, papules, vesicles, urticarial lesions, bullae, eczematous plaques, and erythema multiforme-like lesions. Herein, we present a case of a 30-year-old woman with attacks of edema and erosions involving the oral and genital mucosal sites on every first day of her menstruation period. She had also multiple endocrinological problems such as hypotroidism and infertility. To determine the sex hormon sensitivity, intradermal skin tests were performed. Based on her personal history and skin test findings, a diagnosis of autoimmune estrogen dermatitis was made. After the oophorectomy, she was free from the skin and mucosal symptoms. We propose that it is important to suspect the diagnosis of autoimmune estrogen dermatitis in patients who present with recurrent cylic eruptions and it must be kept in mind that these patients might have a concomitant infertility.

Topics: Adult; Autoimmune Diseases; Biopsy; Dermatitis; Estrogen Antagonists; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hypothyroidism; Infertility; Leuprolide; Menstrual Cycle; Mouth Mucosa; Ovariectomy; Pain; Pruritus; Skin; Skin Tests; Tamoxifen

To compare outcomes of in vitro fertilization (IVF) cycles with adequate versus inadequate response to the gonadotropin-releasing hormone (GnRH) agonist trigger rescued with the use of human chorionic gonadotropin (hCG) retrigger, and to identify risk factors associated with an inadequate trigger.. Retrospective cohort study.. Private practice.. Women at high risk for ovarian hyperstimulation syndrome who underwent an autologous IVF cycle and used GnRH agonist to trigger oocyte maturation before oocyte retrieval.. Patients were triggered with GnRH agonist for final oocyte maturation before retrieval. Patients with an inadequate response, defined by low post-trigger serum LH and P concentrations or failure to recover oocytes after aspiration of several follicles, were retriggered with hCG.. Number of oocytes retrieved, fertilization rate, clinical pregnancy, and live birth.. Two percent of patients triggered with GnRH agonist had an inadequate response and were retriggered with hCG. There was no statistically significant difference in clinical outcomes between the cycles that were retriggered with hCG and successful GnRH agonist triggers. Low body mass index, low baseline LH, and higher total dosage of gonadotropins required for stimulation were associated with an increased risk of having an inadequate response to the GnRH agonist trigger.. A small minority of patients triggered with GnRH agonist had an inadequate response. Rescheduling of oocyte retrieval after hCG retrigger yielded similar IVF outcomes. Evaluation of trigger response based on serum LH and P concentrations is time dependent. Patient characteristics suggestive of hypothalamic hypofunction were predictive of an inadequate response to the GnRH agonist trigger.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Leuprolide; Live Birth; Luteinizing Hormone; Oocyte Retrieval; Oocytes; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Retreatment; Retrospective Studies; Risk Factors; Treatment Failure

A total of 413 consecutive infertile patients (572 cycles) with a body mass index (BMI) of ≥ 25 kg/m(2) were enrolled into the study. The luteal-long GnRH agonist group (Group I) constituted 211 patients (300 cycles) and the flexible-multidose GnRH antagonist group (Group II) constituted 202 patients (272 cycles). The duration of stimulation (d) (10.1 ± 2.5 vs. 9.2 ± 2.0; p < 0.01); the total dose of gonadotrophin used (IU) (3,099.4 ± 2,885.0 vs. 2,684.0 ± 1,046.4; p < 0.05) and the E2 level on the day of hCG (pg/ml) (2,375.8 ± 1,554.6 vs. 1,905.6 ± 1,598.8; p < 0.01) were significantly lower in Group II when compared with Group I. However, the ongoing pregnancy per embryo transfer (37.0% vs. 25.7%; p < 0.05) and the implantation rate (25.7% vs. 15.6%; p < 0.01) were significantly lower in Group II when compared with Group I. In conclusion, we noted that the luteal-long GnRH agonist protocol produced higher implantation rates and higher clinical-ongoing pregnancy rates in overweight and obese patients when compared with the flexible-multidose GnRH antagonist protocol.

Topics: Adult; Clinical Protocols; Contraceptives, Oral, Hormonal; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility; Leuprolide; Luteal Phase; Obesity; Overweight; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted; Retrospective Studies; Time Factors

The objective of this study was to assess the relationship between BMI and oocyte number and maturity in participants who underwent minimal stimulation (mini-) or conventional IVF.. Participants who underwent their first autologous cycle of either conventional (n = 219) or mini-IVF (n = 220) were divided according to their BMI to analyze IVF outcome parameters. The main outcome measure was the number of oocytes in metaphase II (MII). Secondary outcomes included the number of total oocytes retrieved, fertilized (2PN) oocytes, cleavage and blastocyst stage embryos, clinical pregnancy (CP), and live birth (LB) rates.. In conventional IVF, but not in mini-IVF, the number of total oocytes retrieved (14.5  ±  0.8 versus 8.8  ±  1.3) and MII oocytes (11.2 ± 0.7 versus 7.1 ± 1.1) were significantly lower in obese compared with normal BMI women. Multivariable linear regression adjusting for age, day 3 FSH, days of stimulation, and total gonadotropin dose demonstrated that BMI was an independent predictor of the number of MII oocytes in conventional IVF (p = 0.0004). Additionally, only in conventional IVF, BMI was negatively correlated with the total number of 2PN oocytes, as well as the number of cleavage stage embryos.. Female adiposity might impair oocyte number and maturity in conventional IVF but not in mini-IVF. These data suggest that mild ovarian stimulation might yield healthier oocytes in obese women.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility; Leuprolide; Linear Models; Menotropins; Metaphase; Obesity; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Rate

To identify risk factors for a suboptimal response to gonadotropin-releasing hormone (GnRH) agonist trigger in in vitro fertilization (IVF) cycles.. Retrospective cohort study.. Academic medical center.. All 424 patients undergoing fresh IVF cycles (n = 500) between August 2007 and June 2013 in whom a GnRH agonist was used as all or part of the ovulation trigger.. GnRH-antagonist-based IVF cycles triggered with leuprolide acetate alone or in combination with low-dose human chorionic gonadotropin.. Suboptimal response to GnRH-agonist trigger, as defined by a serum luteinizing hormone (LH) level <15 mIU/mL on the morning after trigger.. The rate of suboptimal response to the GnRH-agonist trigger was 5.2%. Patients with a suboptimal hormone response had lower follicle-stimulating hormone (<0.1 vs. 3.48) and LH (<0.1 vs. 2.51) levels on day 2 of the cycle start, lower LH (0.109 vs. 0.596) on the day of trigger, and required longer stimulation and more gonadotropins than those with an adequate response. Suboptimal responders were also more likely to have irregular menses and be on long-term oral contraception. Patients with an undetectable LH on the day of trigger had a 25% chance of a suboptimal LH surge. In our study cohort, limiting the use of the GnRH-agonist trigger alone to patients with a trigger day LH ≥0.5 would have reduced the rate of suboptimal response from 5.2% to 0.2%.. Long-term hormonal contraception use is an independent risk factor for suboptimal response to GnRH-agonist trigger. Patients with very low endogenous serum LH levels on the day of LH trigger are at increased risk for a suboptimal GnRH-agonist trigger response. Understanding the at-risk phenotype and using trigger day LH as a marker for increased risk of suboptimal GnRH-agonist trigger response can be helpful for individualizing treatment and selecting a safe and efficacious trigger medication for patients undergoing IVF.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Contraceptives, Oral, Hormonal; Drug Therapy, Combination; Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Leuprolide; Luteinizing Hormone; Menstruation Disturbances; Pregnancy; Retrospective Studies; Risk Factors; Treatment Failure

Topics: Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Leuprolide; Pregnancy

To analyze the influence of oral contraceptive pill (OCP) pretreatment in intracytoplasmic sperm injection cycles among normoresponders in whom leuprolide acetate is preferred for that kind of gonadotropin-releasing hormone agonist.. Between March 2001 and January 2010, a total of 821 cycles were pretreated with OCP in luteal-long leuprolide acetate in the IVF Center, Faculty of Medicine, University of Hacettepe. Of these, a total of 169 consecutive patients were selected for the final analyses according to the selection criteria (OCP group) and compared with 349 age-matched controls (Control group). The normoresponders were defined by the presence of 6-15 antral follicles in both ovaries.. Female age, body mass index, duration of infertility and antral follicle count were similar among both groups. Although the total dose of FSH used and duration of stimulation were similar, the maximal serum estradiol concentrations were higher in the OCP group than in the Control group (2,630.3 ± 1,568.0 vs. 2,166.5 ± 1,259.7 pg/ml, p = 0.001). The mean numbers of metaphase-II oocytes were 11.0 ± 6.2 versus 9.4 ± 5.2 in the OCP and Control groups, respectively (p = 0.004). The mean number of available day 3 embryos having ≥7 blastomeres was also higher in the OCP group (4.4 ± 3.3 vs. 3.5 ± 3.1, p = 0.013). However, the embryo transfer cancellation rate was noted to be higher in the OCP group, which is mainly due to fertilization failure and arrest during embryogenesis (6.5 vs. 2.9%, p = 0.049). The clinical pregnancy (36.7 vs. 38.3%) and implantation rates (21.8 vs. 20.6%) were comparable.. These findings suggest that although pretreatment with an OCP might exaggerate ovarian response, the pregnancy rate does not fluctuate in leuprolide acetate cycles among normoresponders.

Topics: Adult; Case-Control Studies; Contraceptives, Oral; Drug Therapy, Combination; Embryo Implantation; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Humans; Infertility; Leuprolide; Ovarian Follicle; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic

The aim of this study was to evaluate the relationship of oestradiol level on the day of hCG (peak E2)/oocyte ratio and the outcome of ART cycles. Of the patients who underwent IVF-ET, 600 normal and high responders to the first cycle of COH with gonadotropin releasing hormone (GnRH)-agonist were included in the study. Patients were designated into three groups based on peak E2/oocyte ratio (Group A: <100 pg/ml per oocyte, Group B: 100-200 pg/ml per oocyte, Group C: >200 pg/ml per oocyte). A comparison among groups was made regarding ovarian stimulation characteristics, fertilisation, implantation and pregnancy rates. After the division based on E2/oocyte ratio, in Group C, the number of oocytes retrieved, 2PN and M2 oocyte were statistically lower than both of the other two groups (p = 0.001, 0.001, 0.001, 0.045). HCG day E2 level was significantly different in all groups (p = 0.001), and fertilisation rate was meaningfully highest in Group C and lowest in Group A (p = 0.001). No difference existed among the three groups with respect to the number of embryos transferred and implantation rates. However, clinical pregnancy rate was significantly lower in Group A than others (p = 0.04). In ART cycles suppressed by GnRH-agonist, IVF outcomes are lower in patients with an E2/oocyte proportion of <100 pg/ml per oocyte.

Topics: Adolescent; Adult; Algorithms; Chorionic Gonadotropin; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Leuprolide; Medical Records; Oocytes; Oogenesis; Ovulation Induction; Pregnancy; Pregnancy Rate; Reproductive Techniques, Assisted; Retrospective Studies; Young Adult

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

Topics: Adult; Drug Administration Schedule; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic

There are still some patients who show poor response to ovarian stimulation prior to evidence of normal ovarian reserve in vitro fertilization. However, there are few studies about how to treat the unexpectedly ovarian poor responder in vitro fertilization. The main aim of this study evaluate the effect of prolonging administration follicle-stimulating hormone in woman with the unexpectedly ovarian poor responder in vitro fertilization on implantation rate, clinical pregnancy rate and live birth rate.. 922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups.. The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C.. Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.

Topics: Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropins; Humans; Infertility; Leuprolide; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Time Factors; Treatment Failure; Treatment Outcome

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

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

This report describes a patient who experienced a generalized allergic reaction to Pergonal during controlled ovarian hyperstimulation in preparation for an intracytoplasmic sperm injection procedure for treatment of severe male factor infertility. The report describes a successful desensitization protocol which allowed the patient to complete her treatment cycle despite the allergic reaction to Pergonal. Subsequently recombinant follicle stimulating hormone was used successfully in inducing follicular growth in the absence of any allergic reactions. Therefore, this report confirms other studies which have suggested that an allergic reaction to human menopausal gonadotropins is due to impurities in such urine-derived products.

Topics: Adult; Drug Hypersensitivity; Embryo Transfer; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Humans; Infertility; Leuprolide; Male; Menotropins; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy, Tubal; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Ultrasonography

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

Leuprolide acetate (Lupron) belongs to the group of gonadotrophin-releasing hormone agonists (GnRHa). It is used in conjunction with human menopausal gonadotrophin (HMG) and/or follicle stimulating hormone (FSH) for ovarian stimulation in the so-called ultra-short, short or long protocols. In our programme, the long protocol is mainly used, which starts routinely with s.c. administration of Lupron, 1 mg/day, from day 21 of the cycle preceding ovum retrieval. After pituitary desensitization is achieved, gonadotrophin administration is started. However, unexpected, spontaneous pregnancy may occur during the flare-up phase of Lupron administration. We present six pregnancies and four deliveries which have occurred under these circumstances. The mechanisms by which pregnancy may occur and escape from luteolytic, abortifacient and teratogenic effects of prolonged use of GnRHa are discussed, as well as pregnancy outcome.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Female; Humans; Infant, Newborn; Infertility; Leuprolide; Luteal Phase; Luteolysis; Ovulation Induction; Pregnancy; Pregnancy Outcome; Progesterone; Teratogens

To examine the effect of high doses of gonadotropins on IVF outcome in normal (intermediate) responders.. Retrospective analysis of patients undergoing IVF therapy from 1990 to 1994 at our institution.. Academic tertiary center.. A homogeneous group of women that consisted of intermediate responders examined in their initial attempt and who received differing amounts of gonadotropins were examined.. All patients were stimulated using a combination of a GnRH-agonist and FSH and hMG and were allocated into two groups, based on the amount of gonadotropin administered initially (four or six ampules).. Implantation and pregnancy (clinical and ongoing) rates were compared.. There were no significant differences between patients receiving high doses versus those patients receiving lower doses of gonadotropins with regard to implantation and pregnancy rates.. We conclude that high doses of gonadotropins have no detrimental effect on IVF outcome in normal (intermediate) responders.

Topics: Adult; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Leuprolide; Menotropins; Pregnancy; Retrospective Studies

Serum concentrations of androstenedione, testosterone and dehypdroepiandrosterone sulfate (DHEAS) as well as estradiol and progesterone were measured throughout the in vitro fertilization (IVF) cycle and compared by conception outcome to try to determine if differing levels of androgens could help elucidate the endocrine environment conducive to successful IVF cycles. The luteal phase gonadotropin-releasing hormone agonist (GnRH-a) protocol was used for ovarian stimulation. of the 46 women enrolled in the study, 11 conceived and 35 did not conceive. Throughout the follicular phase, levels of androstenedione and DHEAS were found to rise but the same pattern of increase was found in both conception and non-conception cycles. The pattern of testosterone increase in non-conception cycles was faster than that in conception cycles. Differences in mean levels of androstenedione, testosterone, estradiol and progesterone by conception outcome in the late luteal phase can be attributed to secretion by the corpus luteum. It is possible that those women having multiple failed cycles with rapidly rising serum testosterone levels should be considered for longer use of the GnRH-a. Differences in the pattern of testosterone rise should be monitored.

Topics: Adult; Androgens; Androstenedione; Chorionic Gonadotropin; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Fertilization in Vitro; Follicular Phase; Humans; Infertility; Leuprolide; Luteal Phase; Menotropins; Ovulation Induction; Pregnancy; Progesterone; Testosterone

Leuprolide acetate (LA) has improved the efficiency of human menopausal gonadotropins (hMG) in in vitro fertilization cycles. We hypothesized that the combination of LA/hMG/intrauterine insemination (IUI) would be more efficacious than hMG/IUI cycles.. During an 18-month period, all patients completing either a hMG/IUI cycle (group I) or a LA/hMG/IUI cycle (group II) had the characteristics and outcomes of their stimulation cycles assessed. The groups were not prospectively randomized.. Referral center at a tertiary care hospital.. One hundred twenty three patients in group I completed 219 cycles, and 64 patients in group II completed 102 cycles. Twenty-eight of the patients who failed to conceive with hMG/IUI were advanced to group II.. Pregnancy/IUI is compared between the two groups.. Group II demonstrated significantly greater clinical pregnancy/IUI than group I (26.5% and 16.0%, respectively, P less than 0.05), as well as a higher live birth/IUI (21.6% and 12.8%, respectively, P less than 0.05). No difference was present in the rate of fetal wastage or multiple births.. In our patients with recalcitrant infertility, the addition of a gonadotropin-releasing hormone agonist to hMG/IUI improved the pregnancy rate, without increasing the rate of multiple births or fetal wastage.

Topics: Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Insemination, Artificial; Leuprolide; Male; Menotropins; Ovary; Pregnancy; Pregnancy, Multiple

The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle-stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases.

Topics: Adult; Amenorrhea; Estrogens; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormones; Humans; Infertility; Leuprolide; Menotropins; Middle Aged; Ovulation Induction; Pregnancy; Pregnancy Outcome; Time Factors

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Child; Danazol; Epithelium; Estradiol; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility; Leuprolide; Luteinizing Hormone; Male; Mechlorethamine; Organ Size; Pituitary Hormone-Releasing Hormones; Prednisone; Procarbazine; Rats; Rats, Inbred Strains; Spermatogenesis; Testis; Testosterone; Vincristine

The chemical structure of luteinizing-hormone-releasing hormone (LHRH) was discovered in 1971 after more than a decade of intensive effort. Subsequent physiologic studies in primates and humans showed that the biologic activity of LHRH depends on the way in which the hormone is administered. Pulsatile administration of LHRH, which mimics the natural secretory pattern, causes sustained secretion of the gonadotrophins. This method of administration has been used to induce ovulation in women with hypothalamic amenorrhea and to induce puberty and spermatogenesis in men with hypogonadotrophic hypogonadism. Continuous infusion, however, produces only transient stimulation of gonadotrophin secretion, followed by a "desensitization" response in which gonadotrophin secretion is inhibited. Thus, LHRH can either augment or inhibit gonadotrophin secretion depending on the mode of administration. Recently, long-acting synthetic analogs of LHRH have been shown to desensitize the pituitary gland and inhibit gonadotrophin release when administered as a single daily subcutaneous injection. These LHRH analogs have proved highly effective in the treatment of prostatic carcinoma and central precocious puberty. They are also being studied as a new approach to contraception and to the treatment of endometriosis and polycystic ovary syndrome.

Topics: Animals; Child; Contraceptive Agents, Male; Endometriosis; Estrogens; Female; Follicle Stimulating Hormone; Genital Diseases, Female; Genital Diseases, Male; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamic Diseases; Infertility; Leuprolide; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Ovulation Induction; Polycystic Ovary Syndrome; Prostatic Neoplasms; Puberty, Precocious; Spermatogenesis; Time Factors; Triptorelin Pamoate