trelstar and Infertility

The effects of gonadotrophin-releasing hormone agonist (GnRH-a) administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes.. The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR) per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures.. All cycles presented statistically significantly higher rates of implantation (P<0.0001), CPR per transfer (P=0.006) and ongoing pregnancy (P=0.02) in the group that received luteal-phase GnRH-a administration than in the control group (without luteal-phase-GnRH-a administration). When meta-analysis was carried out only in trials that had used long GnRH-a ovarian stimulation protocol, CPR per transfer (P=0.06) and ongoing pregnancy (P=0.23) rates were not significantly different between the groups, but implantation rate was significant higher (P=0.02) in the group that received luteal-phase-GnRH-a administration. On the other hand, the results from trials that had used GnRH antagonist multi-dose ovarian stimulation protocol showed statistically significantly higher implantation (P=0.0002), CPR per transfer (P=0.04) and ongoing pregnancy rate (P=0.04) in the luteal-phase-GnRH-a administration group. The majority of the results presented heterogeneity.. These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Topics: Algorithms; Dose-Response Relationship, Drug; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteal Phase; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. We studied the possible protective effect of testosterone and triptorelin to inhibit gonadal activity in men and women receiving cyclophosphamide, respectively.. Nonrandomized trial.. 28 consecutive patients, 11 men and 17 women, from a university medical center with various forms of glomerulonephritis, treated with cyclophosphamide.. Men received cyclophosphamide plus testosterone; women were divided into 2 groups: 13 patients (group A) received cyclophosphamide plus triptorelin; 4 (group B) received only cyclophosphamide.. Serum follicle-stimulating hormone (FSH) and serum luteinizing hormone levels and, in addition, sperm counts and testosterone levels in men and estradiol levels in women were measured before and after treatment with cyclophosphamide.. All 10 men became azoospermic or severely oligospermic during treatment; after 12 months, all except 1 had a normal sperm count and FSH levels were normal. In women during cyclophosphamide therapy, amenorrhea occurred in all patients. After cessation of therapy, all women in group A started to menstruate regularly, and at the end of follow-up, ovulatory cycles were demonstrated in all women. Hormone levels showed no significant changes throughout the observation period. Six women conceived, and the pregnancies were brought to term successfully without complications. In group B, all 4 women developed sustained amenorrhea; serum FSH and luteinizing hormone levels at the end of therapy and follow-up were significantly higher with respect to baseline; estradiol levels at the end of follow-up were significantly lower compared with baseline and corresponding values in group A.. The substudy in men is uncontrolled, the substudy in women is nonrandomized.. The study suggests a protective effect of testosterone and triptorelin against cyclophosphamide-induced gonadal damage in men and women with various forms of kidney disease, respectively.

Topics: Adolescent; Adult; Cyclophosphamide; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Infertility; Male; Middle Aged; Prospective Studies; Testosterone; Triptorelin Pamoate

Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied.. Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis.. This trial has been assigned the following registry number: NCT03006406 .

Topics: Adult; Birth Rate; Endometriosis; Female; Humans; Infertility; Luteolytic Agents; Pregnancy; Pregnancy Rate; Prospective Studies; Single-Blind Method; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

To determine the optimal GnRH agonist dose for triggering of oocyte maturation in oocyte donors.. Single-center, randomized, parallel, investigator-blinded trial.. IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam.. One hundred sixty-five oocyte donors (aged 18-35 years, body mass index [BMI] <28 kg/m(2), antimüllerian hormone level >1.25 ng/mL, and antral follicle count ≥6).. Ovulation trigger with 0.2, 0.3, or 0.4 mg triptorelin in a GnRH antagonist cycle.. The primary end point was number of metaphase II oocytes. Secondary end points were fertilization and cleavage rates, number of embryos and top-quality embryos, steroid levels, ovarian volume, and ongoing pregnancy rate (PR) in recipients.. There were no significant differences between the triptorelin 0.2, 0.3, and 0.4 mg trigger groups with respect to number of metaphase II oocytes (16.0 ± 8.5, 15.9 ± 7.8, and 14.7 ± 8.4, respectively), embryos (13.2 ± 7.8, 11.7 ± 6.9, 11.8 ± 7.0), and number of top-quality embryos (3.8 ± 2.9, 3.6 ± 3.0, 4.1 ± 3.0). Luteinizing hormone levels at 24 hours and 36 hours after trigger was significantly higher with triptorelin 0.4 mg versus 0.2 mg and 0.3 mg (9.8 ± 7.1 IU/L vs. 7.3 ± 4.1 IU/L and 7.2 ± 3.7 IU/L, respectively; 4.6 ± 3.2 IU/L vs. 3.2 ± 2.3 IU/L and 3.3 ± 2.1 IU/L, respectively. Progesterone level at oocyte pick-up +6 days was significantly higher in the 0.4-mg group (2.2 ± 3.7 ng/ml) versus 0.2 mg (1.1 ± 1.0 ng/ml) and 0.3 mg (1.2 ± 1.6 ng/ml). One patient developed early-onset severe ovarian hyperstimulation syndrome (OHSS).. No significant differences between triptorelin doses of 0.2, 0.3, and 0.4 mg used for ovulation trigger in oocyte donors were seen with regard to the number of mature oocytes and top-quality embryos.. NCT02208986.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Drug Dosage Calculations; Embryo Transfer; Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Luteinizing Hormone; Metaphase; Oocyte Donation; Oocytes; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Treatment Outcome; Triptorelin Pamoate; Vietnam; Young Adult

Gonadotropin-releasing hormone (GnRH) antagonists for controlled ovarian stimulation (COS) were only recently introduced into China. The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter, controlled, open-label study, in which Chinese women were randomized to either ganirelix (n = 113) or a long GnRH agonist protocol of triptorelin (n = 120). The primary end point was the amount of recombinant follicle-stimulating hormone (rFSH) required to meet the human chorionic gonadotropin criterion (three follicles ≥17 mm). The amount of rFSH needed was significantly lower for ganirelix (1272 IU) vs. triptorelin (1416 IU; P< 0.001). Ongoing pregnancy rates per started cycle were 39.8% (ganirelix) and 39.2% (triptorelin). Although both treatments were well tolerated, cancellation due to risk of ovarian hyperstimulation syndrome (OHSS) was less frequent with ganirelix (1.8%) than triptorelin (7.5%) (P = 0.06). Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol, with fewer reported cases of OHSS and similar pregnancy rates.

Topics: Adult; China; Dose-Response Relationship, Drug; Ectogenesis; Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Incidence; Infertility; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Severity of Illness Index; Triptorelin Pamoate; Young Adult

Prepubertal patients receiving chemotherapy are relatively resistant to cyclophosphamide-induced germinal cell alterations. We studied the possible protective effect of testosterone and triptorelin to inhibit gonadal activity in men and women receiving cyclophosphamide, respectively.. Nonrandomized trial.. 28 consecutive patients, 11 men and 17 women, from a university medical center with various forms of glomerulonephritis, treated with cyclophosphamide.. Men received cyclophosphamide plus testosterone; women were divided into 2 groups: 13 patients (group A) received cyclophosphamide plus triptorelin; 4 (group B) received only cyclophosphamide.. Serum follicle-stimulating hormone (FSH) and serum luteinizing hormone levels and, in addition, sperm counts and testosterone levels in men and estradiol levels in women were measured before and after treatment with cyclophosphamide.. All 10 men became azoospermic or severely oligospermic during treatment; after 12 months, all except 1 had a normal sperm count and FSH levels were normal. In women during cyclophosphamide therapy, amenorrhea occurred in all patients. After cessation of therapy, all women in group A started to menstruate regularly, and at the end of follow-up, ovulatory cycles were demonstrated in all women. Hormone levels showed no significant changes throughout the observation period. Six women conceived, and the pregnancies were brought to term successfully without complications. In group B, all 4 women developed sustained amenorrhea; serum FSH and luteinizing hormone levels at the end of therapy and follow-up were significantly higher with respect to baseline; estradiol levels at the end of follow-up were significantly lower compared with baseline and corresponding values in group A.. The substudy in men is uncontrolled, the substudy in women is nonrandomized.. The study suggests a protective effect of testosterone and triptorelin against cyclophosphamide-induced gonadal damage in men and women with various forms of kidney disease, respectively.

Topics: Adolescent; Adult; Cyclophosphamide; Female; Glomerulonephritis; Humans; Immunosuppressive Agents; Infertility; Male; Middle Aged; Prospective Studies; Testosterone; Triptorelin Pamoate

Although the role that LH plays in folliculogenesis is still controversial, recent evidence points toward facilitatory actions of LH activity in ovulation induction. Thus, we compared the response to either highly purified FSH (75 IU FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist-suppressed women, candidates for intrauterine insemination. A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment; menotropin dose adjustments were allowed thereafter. Treatment was monitored with daily blood samples for the measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG, inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2-day intervals. Although preovulatory E(2) levels were similar, both the duration of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in group B. In the initial 14 treatment days the area under the curve of FSH, progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2 groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B. The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A (60% vs. 17%). We conclude that ovulation induction with LH activity-containing menotropins is associated with 1) shorter treatment duration, 2) lower menotropin consumption, and 3) reduced development of small ovarian follicles. These features can be exploited to develop regimens that optimize treatment outcome, lower costs, and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation.

Topics: Adult; Female; Follicle Stimulating Hormone; Humans; Infertility; Luteinizing Hormone; Menotropins; Ovarian Follicle; Ovulation; Ovulation Induction; Pregnancy; Treatment Outcome; Triptorelin Pamoate

Administration of gonadotrophin-releasing hormone (GnRHa) agonists, used in IVF short-term protocols to initiate follicular recruitment, may be restricted to the early follicular phase without any further risk of LH surge. However, consequences of an early discontinuation upon residual endogenous gonadotrophin secretion are still unknown. Here, the effects of early cessation of GnRH agonist upon gonadotrophin secretion and ovarian parameters of IVF cycles were investigated. A total of 230 normo-ovulatory women were prospectively allocated to one of the two regimens: decapeptyl-GnRH (100 microgram) was daily injected either from day 1 to the triggering of ovulation (group 1) or for the first 7 days (group 2). Exogenous gonadotrophins (150 IU) were administered on day 4 and 5 with a subsequent adjustment. Detections of free alpha subunit and dimeric LH were performed by highly specific 'two site' monoclonal immunoradiometric assays. The results show that early discontinuation of GnRH agonist administration was associated with a sharp decrease in both plasma free alpha subunit and dimeric LH concentrations while plasma oestradiol response to exogenous gonadotrophins was reduced. Other ovarian parameters and pregnancy rate were unchanged. These data indicate that endogenous LH secretion is maintained by a daily administration of GnRH agonist and may contribute to the final follicular maturation.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Glycoprotein Hormones, alpha Subunit; Gonadotropins; Humans; Infertility; Luteinizing Hormone; Oocytes; Ovulation Induction; Pregnancy; Treatment Outcome; Triptorelin Pamoate

To compare the clinical outcomes of modified natural cycle (mNC) and artificial cycle (AC) protocols for frozen embryo transfers.. A total of 490 frozen-thawed autologous embryo transfer cycles, performed in a single tertiary IVF center, between January 2015 and September 2017, were retrospectively analyzed. Of these, 214 cycles were performed after mNC and 276 cycles were performed after gonadotrophin-releasing hormone (GnRH) agonist plus sequential estrogen and progestin priming protocol. The primary outcome was live birth and secondary outcomes were clinical pregnancy, implantation and miscarriage rates. Multivariate regression analysis was used to adjust covariates on clinical outcome.. The rates of live birth (33.6 % vs. 29.3 %, respectively), clinical pregnancy (40.2 % vs. 36.6 %, respectively), implantation (32.3 % vs. 28.5 %, respectively), and miscarriage (5.1 % vs. 6.9 %, respectively) were not different between the mNC and AC groups. Multivariate analysis also showed that the method for endometrial preparation had no significant effect on clinical pregnancy and live birth. The adjusted odds ratios (OR) of live births and clinical pregnancies were 0.97 (95 % CI 0.64-1.48) and 0.98 (95 % CI 0.65-1.46) for the AC compared to mNC group. However, there was a significant difference between mNC and AC in cycles in which double embryo transfer was performed. The live birth (48 % vs. 31.4 %P= 0.01) and clinical pregnancy rates (53.9 % vs. 38.8 %, P= 0.02) were significantly higher in the mNC group than the AC group for double embryo transfers.. The live birth and clinical pregnancy rates are comparable between mNC and AC with GnRH agonists in frozen thawed embryo transfer cycles. In ovulatory patients with planned double embryo transfer, mNC can be considered. Further well-designed prospective studies are needed to confirm our results.

Topics: Abortion, Spontaneous; Adolescent; Adult; Cryopreservation; Embryo Implantation; Embryo Transfer; Endometrium; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Live Birth; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate; Young Adult

Are the LH levels at the start of ovarian stimulation predictive of suboptimal oocyte yield from GnRH agonist triggering in GnRH antagonist down-regulated cycles?. LH levels at the start of ovarian stimulation are an independent predictor of suboptimal oocyte yield following a GnRH agonist trigger.. A GnRH agonist ovulation trigger may result in an inadequate oocyte yield in a small subset of patients. This failure can range from empty follicle syndrome to the retrieval of much fewer oocytes than expected. Suboptimal response to a GnRH agonist trigger has been defined as the presence of circulating LH levels <15 IU/l 12 h after triggering. It has been shown that patients with immeasurable LH levels on trigger day have an up to 25% risk of suboptimal response.. In this retrospective cohort study, all patients (n = 3334) who received GnRH agonist triggering (using Triptoreline 0.2 mg) for final oocyte maturation undergoing a GnRH antagonist cycle in our centre from 2011 to 2017 were included. The primary outcome of the study was oocyte yield, defined as the ratio between the total number of collected oocytes and the number of follicles with a mean diameter >10 mm prior to GnRH agonist trigger.. The endocrine profile of all patients was studied at initiation as well as at the end of ovarian stimulation. In order to evaluate whether LH levels, not only at the end but also at the start, of ovarian stimulation predicted oocyte yield, we performed multivariable regression analysis adjusting for the following confounding factors: female age, body mass index, oral contraceptives before treatment, basal and trigger day estradiol levels, starting FSH levels, use of highly purified human menopausal gonadotrophin and total gonadotropin dose. Suboptimal response to GnRH agonist trigger was defined as <10th percentile of oocyte yield.. The average age was 31.9 years, and the mean oocyte yield was 89%. The suboptimal response to GnRH agonist trigger cut-off (<10th percentile) was 45%, which was exhibited by 340 patients. Following confounder adjustment, multivariable regression analysis showed that LH levels at the initiation of ovarian stimulation remained an independent predictor of suboptimal response even in the multivariable model (adjusted OR 0.920, 95% CI 0.871-0.971). Patients with immeasurable LH levels at the start of stimulation (<0.1 IU/l) had a 45.2% risk of suboptimal response, while the risk decreased with increasing basal LH levels; baseline circulating LH <0.5 IU/L, <2 IU/L and <5 IU/L were associated with a 39.1%, 25.2% and 13.6% risk, respectively.. The main limitation of the study is its retrospective design.. This is the largest study of GnRH agonist trigger cycles only, since most of the previous research on the predictive value of basal LH levels was performed in dual trigger cycles. LH values should be measured prior to start of ovarian stimulation. In cases where they are immeasurable, suboptimal response to GnRH agonist trigger can be anticipated, and an individualized approach is warranted.. There was no funding and no competing interests.. Not applicable.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Oocyte Donation; Oocyte Retrieval; Oocytes; Oogenesis; Ovulation Induction; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

Objectives Gonadotropin-releasing hormone (GnRH) agonists like deslorelin are being increasingly used in tom cats for their efficacy in controlling reproductive behaviour and fertility. Deslorelin implants have been widely available in Europe since 2008. Little, if anything, is known about the interval between treatment and onset of sterility, as well as semen quality, after treatment in tom cats. The purpose of this study was to investigate semen quality and interval to sterility in tom cats treated with a 9.4 mg deslorelin implant. Methods Fifteen healthy adult tom cats were treated with a 9.4 mg deslorelin implant (Suprelorin 12). For each cat, semen collection and a GnRH stimulation test (intramuscular administration of 50 μg gonadorelin [Fertagyl], followed by blood sampling 1 h later, to assay serum testosterone) were performed on the first consultation and then repeated every 15 days until complete sterility was achieved. Semen collection was performed by introducing a 14 cm, open-end feline catheter (Argyle) 9 cm into the distal urethra 10 mins after sedation by intramuscular injection of 100 μg/kg medetomidine (Domitor). Results Semen collection was not successful in all cats at each attempt. In the first month after treatment, the semen of only four cats could be evaluated, while the semen of eight cats could be evaluated during the second and third months of the study. Semen quality (ejaculate volume, progressive motility and morphological abnormalities) improved slightly during the first 19-25 days in 2/4 cats, and in 1/4 cats motility was still very high (80%) 25 days post-treatment (PT), but we have no data regarding fertility prior to treatment in this cat. The last cat never produced spermatozoa. Subsequently, semen quality gradually worsened in all cats from 30 days onwards. At 70 days PT, one cat was still potentially fertile. After 72 days all cats were sterile. Conclusions and relevance Semen quality increased slightly in treated cats during the first month after treatment, and then gradually decreased over the following months. Complete sterility was reached within 40-72 days following implantation.

Topics: Animals; Cat Diseases; Cats; Contraception; Contraceptive Agents, Male; Drug Implants; Infertility; Infertility, Male; Male; Semen; Semen Analysis; Sexual Behavior, Animal; Triptorelin Pamoate

Over the last 40 years, researchers have explored methods to non-surgically suppress fertility in animals. Immunocontraception has been used to control wildlife populations but does not confer long-term immunity. The gonadotropin-releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide 6-month to 1-year suppression of fertility in male dogs, is available commercially in some countries. Neither of these approaches provide permanent sterility. A single-dose, permanent treatment would be a valuable tool in dog and cat population control. The Michelson Prize and Grants (MPG) programme was initiated "to eliminate shelter euthanasia of healthy, adoptable companion animals and reduce populations of feral and free-roaming cats and dogs" offering a $25 million US prize for a non-surgical sterilant that is effective as a single treatment in both male and female dogs and cats. Michelson Prize and Grants programme has offered US $50 million in grant money for research and has attracted scientists worldwide. Approaches under study include gene therapy, small interfering RNA to inhibit reproductive targets and delivery of cytotoxins to pituitary gonadotrophs or GnRH producing neurons in the hypothalamus. Research in implant technology that could deliver compounds over an animal's lifetime is also underway. Details of funded grants and results to date can be found at: http://www.michelsonprizeandgrants.org/michelson-grants/research-findings. The next steps are translating the most promising research into products. The Alliance for Contraception of Cats and Dogs (ACC&D) is helping to research practical methods of marking sterilized animals to avoid costly retreatment and population modelling that will help guide field workers in use of resources for sterilization programmes.

Topics: Animals; Awards and Prizes; Cats; Contraception; Contraception, Immunologic; Contraceptive Agents; Cytotoxins; Dogs; Drug Implants; Female; Gene Silencing; Gonadotropin-Releasing Hormone; Infertility; Male; Population Control; Research Support as Topic; RNA, Small Interfering; Sterilization, Reproductive; Triptorelin Pamoate

To investigate the messenger RNA (mRNA) expression of reproduction-related genes in granulosa cells (GCs) of patients triggered with hCG compared with patients triggered with GnRH agonist and hCG (double trigger) for final oocyte maturation.. Granulosa cells were obtained at the time of oocyte retrieval, and gene expression was analyzed using quantitative real-time polymerase chain reaction.. Referral center.. Fifteen women undergoing controlled ovarian hyperstimulation for IVF who received hCG for final follicular maturation and in a subsequent IVF cycle received double trigger.. Granulosa cells collection.. The expression of genes related to ovarian hyperstimulation syndrome, gap junction, and epidermal-like growth factor in GCs.. The mRNA expressions of amphiregulin (2.1 vs. 1, arbitrary unit) and epiregulin (2.5 vs. 1, arbitrary unit) were significantly higher in the double trigger group compared with the hCG group. We found no difference in luteinizing hormone receptor and follicle stimulating hormone receptor mRNA expressions between the two groups. Moreover, although the mRNA expression of pigment epithelium-derived factor (1.5 vs. 1, arbitrary unit) was significantly higher in the double trigger group, no between-group differences were observed in the expression of vascular endothelial growth factor and GnRH receptor. The mRNA expression of conexin43 in cumulus cells (0.7 vs. 1, arbitrary unit) was significantly lower in the double trigger group compared with the hCG group.. Our findings suggest that the decreased expression of conexin43 and the increased expression of epiregulin and amphiregulin in the GCs from patients receiving the double trigger may explain the suggested improved oocyte and embryo quality related to the double triggering group.

Topics: Adult; Amphiregulin; Chorionic Gonadotropin; Connexin 43; Drug Therapy, Combination; Epiregulin; Female; Fertility; Fertility Agents; Fertilization in Vitro; Gene Expression Regulation, Developmental; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Infertility; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Prospective Studies; RNA, Messenger; Triptorelin Pamoate

To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET).. Retrospective cohort study.. University-affiliated hospital.. Normogonadotropic women undergoing IVF.. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol.. Live-birth rate per fresh ET.. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol.. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Embryo Implantation; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hospitals, University; Humans; Infertility; Live Birth; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Retrospective Studies; Time Factors; Treatment Outcome; Triptorelin Pamoate

To explore the effects of overweight and obesity on the outcomes of in vitro fertilisation (IVF) in Chinese infertile patients.. A retrospective cohort study was carried out in 2222 normal weight (18.5 or= 30) women who underwent their first IVF cycles between 2002 and 2008. Cycle characteristics and IVF outcomes were analysed.. Obese women required significantly higher dose of rFSH (3272 IU vs. 2587 IU, p < 0.001) and days of stimulation (11.89 +/- 4.57 vs. 10.42 +/- 2.03, p < 0.001), but exhibited less oocytes retrieved and significantly lower fertilisation rate (54.1% vs. 61.1%, p < 0.001) than normal weight women. Compared with normal weight women, overweight women displayed significantly less oocytes retrieved (12.98 +/- 6.91 vs. 14.49 +/- 7.96, p < 0.001), lower fertilisation rate (60.8 +/- 23.3 vs. 61.1 +/- 23.0, p < 0.001), less cleavaged embryos (7.55 +/- 4.86 vs. 8.67 +/- 5.90, p < 0.001), less high-grade embryos (4.65 +/- 3.96 vs. 5.59 +/- 4.81, p < 0.001) and cryopreserved embryos (4.44 +/- 4.55 vs. 5.49 +/- 5.55, p < 0.001). All parameters of pregnancy outcomes, including pregnancy rate, miscarriage rate and live birth rate, were comparable among three groups.. Overweight and obesity are related with impared ovarian response, and negatively affect the outcomes of IVF.

Topics: Adult; Body Mass Index; China; Cohort Studies; Cryopreservation; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Obesity; Oocytes; Overweight; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Retrospective Studies; Sperm Injections, Intracytoplasmic; Tissue and Organ Harvesting; Treatment Outcome; Triptorelin Pamoate

This report is to illustrate two cases of ovarian hyperstimulation syndrome following the sole administration of injectable mid-luteal gonadotropin-releasing hormone agonists (triptorelin) for pituitary down-regulation. Both women underwent egg retrieval, and despite the transfer of good quality embryos, no pregnancy was achieved. The possible mechanism and management of the condition were discussed.

Topics: Adult; Embryo Transfer; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Luteinizing Hormone; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Progesterone; Treatment Failure; Triptorelin Pamoate; Ultrasonography

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

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Triptorelin Pamoate

This retrospective study was performed to examine the implantation and pregnancy rates of frozen-thawed pronuclear stage oocytes obtained with the use of a GnRH antagonist, Cetrorelix (Cetrotide((R)) ASTA-Medica, Frankfurt/M, Germany) used in a multidose protocol with hMG, and to compare these results with those obtained after a conventional long GnRH analogue protocol (Decapeptyl-Depot, Ferring, Kiel, Germany). The study population consisted of 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the GnRH antagonist Cetrorelix (Cetrorelix((R))) and 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the long GnRH analogue protocol. Patients underwent ICSI after down regulation with a GnRH agonist (Decapeptyl) and stimulation with hMG, or a GnRH antagonist (Cetrorelix) and hMG. The supernumerary pronuclear stage oocytes were cryopreserved and transferred in a later mildly stimulated cycle. The implantation and pregnancy rates for frozen-thawed pronuclear stage oocytes derived from the GnRH antagonist compared with the GnRH agonist were 3.26% versus 3.73% (P=1.0000) and 8.33% versus 10.25% (P=1.0000), respectively. To our knowledge we report here the first pregnancies obtained by the transfer of cryopreserved pronuclear stage embryos generated from ICSI using a GnRH antagonist in the collecting cycle. The use of Cetrorelix in a multiple dose protocol in combination with hMG does not demonstrate a negative effect on viability, implantation potential or pregnancy outcome as compared to 2PN conceptuses obtained from a long GnRH agonist-hMG protocol.

Topics: Abortion, Spontaneous; Cryopreservation; Embryo Implantation; Embryo Transfer; Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Menotropins; Oocytes; Pregnancy; Pregnancy Outcome; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

The role of transvaginal pulsed colour Doppler ultrasound in the assessment of ovarian vascularity was studied in 196 in-vitro fertilization (IVF) cycles. The changes in ovarian blood flow after gonadotrophin-releasing hormone agonist (GnRHa) down-regulation and human menopausal gonadotrophin (HMG) stimulation were determined. The data obtained showed that the ovarian blood flow was significantly improved by oestradiol secretion (P = 0.05) and human chorionic gonadotrophin (HCG) administration (P = 0.003). Folliculogenesis was affected by blood flow supply. The resistance index (RI) value was significantly different (P = 0.05) according to the duration of ovarian stimulation. Patients with a mean RI value >0.56 had a longer stimulation with a significantly lower mean number of oocytes retrieved (P = 0.01) despite the administration of a standard dose of HMG. The RI value is a good indicator of modifications in ovarian vascularization during stimulation. Doppler blood flow measurement could be used to determine the optimal timing for the beginning of HMG administration in patients undergoing ovarian stimulation after down-regulation for IVF treatment.

Topics: Adult; Blood Flow Velocity; Chorionic Gonadotropin; Drug Resistance; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Menotropins; Ovary; Ovulation Induction; Pregnancy; Time Factors; Triptorelin Pamoate; Ultrasonography

This study aimed to standardize the clomiphene citrate test (CC-t) in our laboratory while comparing two different protocols of controlled ovarian stimulation in poor responders. One hundred and forty-four patients scheduled for assisted reproductive techniques were submitted to the CC-t within 3 months before starting stimulation; 133 underwent controlled ovarian stimulation with a blocking protocol. Poor responders in the first cycle (n = 30) were subsequently treated with a flare-up protocol. Although it was not statistically significant, more patients reached oocyte retrieval with the flare-up protocol. In the completed cycles, more gonadotropin ampules (55 +/- 15 vs. 34 +/- 13; p < 0.001) and more stimulation days (12.6 +/- 1 vs. 11.6 +/- 1.2; p < 0.005) were needed in the blocking than in the flare-up protocol. No difference was observed in peak 17 beta-estradiol levels, preovulatory follicles, oocytes retrieved or pregnancy rate between the two protocols. According to the threshold values, established on CC-t of patients who obtained a clinical pregnancy (n = 44), the incidence of abnormal results was 10%. All but one patient with abnormal CC-t were poor responders during the first stimulation cycle. The flare-up protocol did not improve the ovarian response in these patients.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Clomiphene; Desogestrel; Embryo Transfer; Estradiol; Ethinyl Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gamete Intrafallopian Transfer; Humans; Infertility; Menotropins; Ovulation Induction; Pregnancy; Triptorelin Pamoate

The timing of ovulation induction is usually decided according to estradiol plasma concentrations and follicle size. We administered human chorionic gonadotropin (hCG) when at least three follicles of 16 mm or more in diameter and adequate estradiol plasma concentrations were detected. We studied the percentage of mature oocyte-cumulus-corona radiata complexes, estradiol and progesterone concentrations in a heterogeneous sized follicle population (range 10-20 mm, n = 90) to perform a retrospective analysis of the adequacy of criteria adopted for the timing of ovulation induction. Plasma and follicular fluid were obtained from 20 normo-ovulating women (aged 28-37 years) treated with gonadotropin releasing hormone analogs (GnRH-a) and human menopausal gonadotropin (hMG) for in vitro fertilization (IVF). No correlation was found between the mean individual follicular fluid estradiol concentration (500-5640 nmol/l) and the respective maximum concentration in plasma (2-16 nmol/l). The estradiol concentration was similar in all follicles. Total follicular fluid estradiol concentration was found to be correlated with follicular fluid volume (r = 0.771, p < 0.01). On the day of hCG administration, the concentration of estradiol in the plasma but not the follicular fluid was correlated with the number of oocyte-cumulus-corona radiata complexes collected (p < 0.01) and the number of mature complexes (p < 0.01). At oocyte pick-up, the plasma concentration of progesterone was correlated (p < 0.01) with number of complexes collected and the number of mature complexes. The percentage of mature complexes collected (77.5%) was higher than suggested by the number of leading follicles. This indicates that our criteria for administering hCG were adequate and that heterogeneous follicle size does not exclude a high rate of mature oocyte-cumulus-corona radiata complexes.

Topics: Adult; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility; Menotropins; Menstrual Cycle; Ovarian Follicle; Progesterone; Steroids; Triptorelin Pamoate

The prognostic value of the oestradiol flare-up in response to gonadotrophin-releasing hormone (GnRH) agonist was evaluated in 140 in-vitro fertilization (IVF) cycles programmed by progestogen pretreatment. Three days after the end of administration of norethisterone, a routinely used short-term DTRP6 GnRH agonist protocol was started (designated day 1), gonadotrophins being introduced from day 4. Serum oestradiol flare-up values were evaluated on days 1, 2 and 3 to study their relationship with the subsequent IVF outcome. On day 2, 87.9% of the cycles exhibited a significant rise in serum oestradiol concentration from baseline (delta E2 > or = 5 pg/ml). Compared to cycles without any significant oestradiol increase, they had a higher pregnancy rate per transfer (33.3 versus 9.1%, P = 0.02), although the number of transferred embryos did not differ significantly. Taking into account the previously described cut-off value (doubling from baseline), we found that less than half of the cycles (45.7%) involved a doubling of oestradiol values during flare-up, and we did not observe any significant difference in IVF outcome in these cycles compared to those without doubling. In conclusion, progestogen pretreatment, by inducing ovarian quiescence, may lower the oestradiol cut-off value that is predictive of the subsequent pregnancy rate. Nevertheless, determination of the absolute oestradiol response (delta E2) to GnRH agonist after progestogen pretreatment could allow a further adaptation of the protocol to achieve an optimum response in each cycle. Another alternative for patients with a lower delta E2 could be the suppression of progestogen pretreatment.

Topics: Adult; Clinical Protocols; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteolytic Agents; Male; Norethindrone; Ovulation Induction; Pregnancy; Progesterone Congeners; Prognosis; Time Factors; Triptorelin Pamoate

The recent use of gonadotrophin-releasing hormone agonist in a short-term regimen has allowed the effectiveness of human menopausal gonadotrophin (HMG) stimulation to be markedly improved. It seems to be related to the flare-up effect of the agonist in the early follicular phase of the cycle. However, individual hormonal responses to the agonist are quite variable and four patterns of oestradiol secretion have been described. The present study indicates that in women pre-treated with progestogen, only two patterns of serum oestradiol are observed in the flare-up period, with a significant increase in 57% of patients. Significant correlations are observed between oestradiol values and the endogenous gonadotrophin surge (positively with luteinizing hormone, r = 0.38; P less than 0.05 and negatively with follicle stimulating hormone, r = 0.48; P less than 0.005). Furthermore, there was a significant relationship between the hormonal flare-up and the ovarian parameters following HMG stimulation. In conclusion, in progestogen-pre-treated women, the serum oestradiol level during the flare-up period is a reliable index to predict subsequent effectiveness of ovarian stimulation with HMG.

Topics: Adult; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Luteinizing Hormone; Menotropins; Norethindrone; Ovary; Triptorelin Pamoate

Attempts have been made to increase the low pregnancy rate in in-vitro fertilization (IVF) cycles by luteal phase support with progesterone or human chorionic gonadotrophin (HCG). Previously, this practice has been inconsistent and the results unclear. The detailed effect of support on the progesterone profile in the luteal phase was assessed by daily salivary progesterone measurements in non-conception IVF cycles. The comparison of HCG and progesterone support in two different stimulation protocols showed that the profile of luteal progesterone concentrations was similar in control cycles and those supported with a vaginal progesterone suppository, showing an early decrease by the fourth luteal day. In cycles supported with multiple doses of HCG, the progesterone profile was normal but slightly increased up to the 9th luteal day subsequently falling to basal levels by the fourteenth luteal day.

Topics: Chorionic Gonadotropin; Clomiphene; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteal Phase; Progesterone; Saliva; Triptorelin Pamoate

It has previously been demonstrated that use of gonadotrophin releasing hormone analogues allows the administration of HCG to be delayed and makes it possible to avoid oocyte retrievals at weekends. In this study, we demonstrate that it is also possible to avoid embryo transfers on Sundays, by delaying transfers of Friday retrievals until Monday, without any apparent change in the results. This facility should improve the cost-effectiveness of assisted reproduction programmes.

Topics: Buserelin; Embryo Transfer; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Menotropins; Ovary; Ovulation Induction; Pregnancy; Pregnancy Outcome; Triptorelin Pamoate

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