trelstar and Ovarian-Hyperstimulation-Syndrome

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

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

To review published randomized controlled trials (RCTs) evaluating the outcomes of in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) utilization of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation in polycystic ovarian syndrome (PCOS) patients compared with classic luteal long agonist protocols.. A meta-analysis of prospective randomized trials published in English between 2002 and 2013.. Nine RCTs examining PCOS patients undergoing IVF/ICSI including 588 women who underwent long agonist protocols and 554 women who underwent GnRH antagonist protocols.. Clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) rate.. Nine RCTs were included in this analysis. The CPR-per-embryo transferred was similar in the two groups (relative risk (RR): 0.97, 95% confidence interval (CI): 0.85-1.10). Non-significant estimates comparing the two protocols were found for age, BMI, total dose of gonadotropin administered, number of days of stimulation and number of oocytes retrieved. After meta-analysis of 4 of the RCTs, it was concluded that a GnRH antagonist protocol is better than an agonist long protocol to reduce the rate of severe OHSS (odds ratio (OR): 1.56, 95% CI: 0.29-8.51).. With respect to CPR, a GnRH antagonist protocol is similar to a GnRH agonist long protocol. However, for severe OHSS, a GnRH antagonist protocol is significantly better in PCOS patients.

Topics: Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility, Female; Luteolytic Agents; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

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

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

Topics: Chorionic Gonadotropin; Clinical Protocols; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Recombinant Proteins; Triptorelin Pamoate

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

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

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

Topics: Buserelin; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Triptorelin Pamoate

Topics: Chorionic Gonadotropin; Drug Administration Schedule; Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Triptorelin Pamoate

Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovarian stimulation. In severe cases, haemoconcentration, hypovolaemia, thromboembolism and death may result. It is reassuring that its incidence is not increased after ovarian stimulation for in-vitro fertilization despite very high serum oestradiol levels and large numbers of follicles and oocytes. This may be related to follicular aspiration, expert monitoring or low implantation rates. However, complete prevention has not been achieved despite the wide availability of ultrasound and oestradiol assays, thus presenting the clinician with a continuous challenge. Our aim is to analyse critically the most recent published series of OHSS in in-vitro fertilization and other assisted reproduction techniques using stimulation with gonadotrophin releasing hormone agonists (GnRHa) and human menopausal gonadotrophin (HMG). The main determining factor in the development of OHSS appears to be ovarian predisposition. Patients with polycystic ovarian disease are at a high risk of OHSS and therefore a small dose and slow start of HMG is recommended, tailoring the dosage according to the ovarian response. Accurate prediction by ultrasound and oestradiol assays and strict prevention by withholding human chorionic gonadotrophin (HCG) or cryopreservation of all the embryos have a major impact on the occurrence of OHSS. It is interesting that fixed-schedule IVF cycles, without detailed monitoring, are not associated with an increased incidence of OHSS. The use of GnRHa, despite expectations, is associated with a higher prevalence of OHSS. Luteal phase supplementation with progesterone rather than HCG should be used in cycles where oestradiol is greater than 2500 ng/l or where the number of oocytes exceeded 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Triptorelin Pamoate

Is a dual ovulation trigger with a combination of GnRH agonist (GnRHa) and hCG superior to single hCG and/or single GnRHa trigger in improving treatment outcomes in advanced-age women (aged ≥ 35 years) undergoing IVF/ICSI treatment?. Co-administration of GnRHa and hCG as a dual trigger increases the number of good-quality embryos but it is not associated with a higher number of oocytes retrieved, compared with single hCG or GnRHa trigger.. Many studies have demonstrated that a dual trigger has positive impact on oocyte maturation, retrieval rate and pregnancy rate without increasing the risk of ovarian hyperstimulation syndrome (OHSS) in some groups of IVF patients, when compared with single hCG trigger. Few studies have however been conducted to compare a dual trigger with a single GnRHa trigger, and insufficient evidence exists to support which trigger can achieve the best outcomes in IVF patients aged ≥35 years.. This was an open-label randomized controlled trial of 510 participants conducted at single reproductive medical center from January 2019 to December 2021. After a sample size calculation performed by retrospectively analyzing our previous clinical data, we planned to recruit 170 patients in each group and 510 patients in total for the study.. Women aged ≥35 years undergoing IVF/ICSI treatment, receiving a non-pituitary down-regulation protocol, and with low risk of OHSS, were enrolled in this trial. On the trigger day, patients were randomized into three groups: hCG alone (who received 6000 IU of hCG), GnRHa alone (who received 0.2 mg of triptorelin) and dual trigger (who received 0.2 mg of triptorelin plus 2000 IU of hCG) groups. The primary outcome parameter was the number of retrieved oocytes. The secondary outcome parameters included, among others, the number and rates of mature oocytes, two pronuclei (2PN) embryos and good-quality embryos, as the rates of OHSS, clinical pregnancy, miscarriage and live birth.. There were no significant differences in the baseline demographic characteristics among the three groups. The dual trigger was associated with a higher retrieval rate (87.9% vs 84.1% in the hCG group, P = 0.031; 87.9% vs 83.6% in the GnRHa group, P = 0.014). However, the number of retrieved oocytes in the dual trigger group was comparable with those in the hCG group (4.08 ± 2.79 vs 3.60 ± 2.71, P = 0.080) and the GnRHa group (4.08 ± 2.79 vs 3.81 ± 3.38, P = 0.101); comparable data between the groups were also found when analyzing the number of 2PN embryos and the 2PN rate. In the dual trigger group, the numbers of good-quality embryos and viable embryos were both significantly higher than in the hCG group (1.74 ± 1.90 vs 1.19 ± 1.45, P = 0.016 and 2.19 ± 2.11 vs 1.56 ± 1.66, P = 0.008, respectively) and the GnRHa group (1.74 ± 1.90 vs 1.20 ± 1.67, P = 0.003 and 2.19 ± 2.11 vs 1.45 ± 1.75, P = 0.001, respectively). Pregnancy outcomes after fresh embryo transfer (ET) were comparable between the groups. The live birth rate and ongoing pregnancy rate after frozen ET in the dual trigger group were significantly higher than those in the GnRHa group (32.6% vs 14.1%, P = 0.007 and 34.8% vs 17.6%, P = 0.013, respectively), but not superior to those in the hCG group (32.6% vs 27.9%, P = 0.537 and 34.8% vs 27.9%, P = 0.358, respectively).. Women of advanced age are quite a heterogeneous population and overlap with poor ovarian responders or patients with diminished ovarian reserve. We therefore could not entirely exclude selection biases or confounding factors. This study was also not a double-blinded trial; the patients in the GnRHa and dual trigger groups could have been affected by the placebo effect.. The results of this study suggest that in advanced-age women with low risk of OHSS, a dual trigger or even a single hCG trigger may be a better choice than a single GnRHa trigger.. This study was supported by the Shanghai Municipal Health Commission of Science and Research Fund (20184Y0289). The authors declare no conflict of interest.. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-1800016285).. 24 May 2018.. 2 January 2019.

Topics: China; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone.. The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions.. A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p < 0,01. No increase of OHSS risk was observed.. From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results.. The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

Topics: Adult; Embryo Implantation; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Live Birth; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Prospective Studies; Risk Factors; Triptorelin Pamoate

Morphological aspect of polycystic ovaries (PCO) is a very common finding in an IVF center population: this includes PCOS patients identified in 18-25% of the couples presenting with infertility and so called "sonographic PCO only" the prevalence of which has been estimated as high as 33% in asymptomatic patients. Finding the optimal first intention IVF protocol for polycystic ovaries patients is still challenging in order to improve the controlled ovarian hyperstimulation (COH) outcome while avoiding ovarian hyperstimulation syndrome (OHSS). It has been suggested that women with PCO would benefit from a longer period of pituitary down-regulation. The purpose of this study was to compare an extended duration of OCP pretreatment with a classic GnRH agonist protocol.. A single center prospective non-randomized study was performed from January 2009 to December 2010 in the Lille University Hospital including 113 women diagnosed with PCO(S) according to the Rotterdam ultrasonographic criteria and undergoing their first IVF attempt. Comprehensive hormonal and ultra-sonographic assessments were collected during COH in these patients. LH and androgen suppression and dynamics of follicular growth were compared between the two protocols as well as the COH outcome in terms of oocyte/embryo number and quality, implantation and pregnancy rates.. No significant difference was observed between the two groups concerning dynamics of follicular growth and hormonal values. Clinical and ongoing pregnancy rates were significantly lower in the OCP group despite same oocyte and embryo quality. Nevertheless, the cumulative pregnancy rate did not differ between the two groups. The incidence of OHSS was not statistically significant.. Extended duration of OCP pretreatment, as a first intention IVF protocol for PCO patients, does not improve the pattern of follicular growth nor the oocyte and embryo quality.

Topics: Adult; Androstenedione; Contraceptives, Oral; Desogestrel; Drug Administration Schedule; Drug Therapy, Combination; Embryo Transfer; Ethinyl Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Testosterone; Treatment Outcome; Triptorelin Pamoate; Ultrasonography; Young Adult

To assess whether, in GnRH agonist IVF cycles where there is a risk of ovarian hyperstimulation syndrome (OHSS), the addition of cabergoline to the hydroxyethyl starch (HES) infusion could decrease OHSS incidence and severity.. Prospective randomized study. The population under study consisted of women undergoing IVF cycles with GnRH agonist protocols, at risk of OHSS (more than 20 follicles observed larger than 12 mm in diameter and/or estradiol levels of 3000-5000 pg/mL). Women received a slow infusion of 500 mL of 6% HES during follicular aspiration alone or combined with 0.5mg cabergoline administration for 8 days, starting on the day of hCG administration.. The rates of OHSS (both early and late) were very similar in the HES alone group (3.19% (3/94)) and in the HES plus cabergoline group (5.68% (5/88)), as were the rates of severe cases of OHSS (1.06% and 2.27%). Pregnancy rates (PR) were also similar in the two groups (ongoing PR per transfer, 47.56% and 47.50%).. The co-administration of cabergoline in patients receiving HES due to OHSS risk did not reduce the rate or severity of OHSS in GnRH agonist IVF cycles.

Topics: Adult; Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Hydroxyethyl Starch Derivatives; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Plasma Substitutes; Pregnancy; Pregnancy Rate; Prospective Studies; Secondary Prevention; Triptorelin Pamoate

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

To prospectively study ovarian hyperstimulation syndrome (OHSS) incidence and cumulative live birth rate in a cohort of patients at risk of OHSS undergoing ovarian stimulation in a GnRH antagonist protocol and receiving a GnRH agonist triggering followed by cryopreservation of all two pronuclei (2PN)-stage zygotes by two methods, vitrification or slow-cooling, for later ET.. Prospective, clinical cohort study.. Five IVF centers in Germany; time frame: June 2008 to June 2010.. Fifty-one female patients undergoing IVF considered at risk of developing severe OHSS (≥20 follicles≥11 mm and/or E2 level≥4,000 pg/mL) after ovarian stimulation in a GnRH antagonist protocol.. Triptorelin (0.2 mg SC) for triggering final oocyte maturation. All 2PN-stage zygotes were cryopreserved by vitrification or slow-cooling for later repetitive frozen-thawed ET.. Severe OHSS incidence and cumulative live birth rate per patient.. Of 51 patients, 1 patient (2%, 95% confidence [CI] 0.3%-10.3%) had zero oocyte retrieved, 1 patient did not undergo frozen-thawed ET, and 1 patient had no surviving oocyte after thawing. Thus, 48 patients underwent at least one frozen-thawed ET. The cumulative live birth rate was 37.3% (19/51, 95% CI 25.3%-51.0%). The live birth rate per first frozen-thawed ET was 5.9% (1/17, 95% CI 10.0%-27.0%) and 19.4% (6/31, 95% CI 9.2%-36.3%) in the slow-cooling and vitrification group, respectively (difference: 13.5%, 95% CI of the difference: -9.9%-31.1%). Three cases of OHSS II (3/51, 5.9%, 95% CI 2.0%-15.9%) and one early-onset case of OHSS III (1/51, 2%, 95% CI 0.3%-10.3%) occurred.. Agonist triggering with cryopreservation is efficacious and safe, although a single case of a severe early-onset OHSS occurred.

Topics: Adult; Female; Fertilization in Vitro; Freezing; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Oocyte Retrieval; Oocytes; Oogenesis; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Triptorelin Pamoate

Aim of this study was to assess the efficacy of recombinant luteinizing hormone (rLH) supplementation in late follicular phase in multiple follicular stimulation with recombinant follicle stimulating hormone (rFSH) in Triptoreline down-regulated patients undergoing IVF, on preventing clinical OHSS and cycles cancellation for OHSS risk. Nine hundred ninety-nine patients aged ≤ 40 with basal FSH ≤ 12 mUI/Ml were down-regulated before starting rFSH stimulation for oocytes recovery. Patients were allocated in two groups: (A) (501 patients) treated with 150 IU of rFSH eventually adjusting rFSH dosage day 7 of stimulation until recombinant human chorionic gonadotropin (rhCG) administration, (B) (498 patients) treated with 150 IU of rFSH and 75 IU of rLH since day 7 of stimulation until rhCG administration and adjusting rFSH at the same day. E2 the day of rhCG was higher in group B (p < 0.0001); number of cycles cancelled in group A (42/8.3%) for risk of ovarian hyperstimulation syndrome (OHSS) was higher than group B (12/2.4%) (p < 0.000001). We observed an increase in pregnancies in group B compared with group A (16.8% vs 11.9%) (p < 0.05) and we observed also a larger number of clinical OHSS in group A than in group B (p < 0.05).

Topics: Adult; Down-Regulation; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Italy; Luteinizing Hormone; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Single-Blind Method; Treatment Outcome; Triptorelin Pamoate

Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized).. In this randomised controlled trial (RCT), 220 patients with PCOS were randomly allocated in two groups: long GnRH agonist down-regulation protocol (n = 110) and flexible GnRH antagonist protocol (n = 110).. No differences were observed in ongoing pregnancy rates [50.9 versus 47.3%, difference 3.6%, 95% confidence interval (CI): -9.6 to +16.8%] in the agonist and antagonist protocols, respectively. Incidence of OHSS Grade II was lower in the antagonist compared with agonist group (40.0 versus 60.0%, difference -20.0%, 95% CI: -7.1 to -32.9%, P < 0.01). Duration of stimulation (10 versus 12 days, difference 2 days, 95% CI: +1 to +2, P < 0.001) and total gonadotrophin required (1575 versus 1850 IU, difference -275 IU, 95% CI: -25 to -400, P < 0.05) were also lower in the antagonist compared with agonist protocol.. The current RCT suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF. The study was registered at clinicaltrials.gov. ID: NCT00417144.

Topics: Adult; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Treatment Outcome; Triptorelin Pamoate

To prospectively study the incidence of OHSS, live birth likelihood and neonatal outcome after GnRH-agonist triggering of final oocyte maturation and vitrification of all pronucleate (2PN) oocytes for later frozen-thawed embryo transfer (FRET) in an OHSS-risk population.. Prospective, clinical cohort study (12/2004-5/2009). Forty patients undergoing ovarian stimulation in a GnRH-antagonist protocol and at risk of developing severe OHSS underwent triggering with 0.2mg triptorelin and elective vitrification of all 2PN-oocytes for later frozen-thawed embryo transfer.. The incidence of OHSS was 0% (0/40; 95% confidence interval: 0.0-6.4%). Thirty-nine patients underwent 87 FRETs (mean number of FRETs per patient: 2.2+/-1.6; range: 1-7). The cumulative live birth rate per patient was 35.0% (14/40; 95% confidence interval: 23.9-48.0%). Mean time-to-conception resulting in live birth after agonist triggering was 24.2 (+/-17.1; range: 9-67) weeks. Nine healthy singletons and five twins were born.. A treatment algorithm combining agonist trigger with vitrification of all 2PN-oocytes is feasible and safe, and provides patients with a good cumulative chance of live birth.

Topics: Adult; Birth Rate; Cohort Studies; Cryopreservation; Embryo Transfer; Female; Humans; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Prospective Studies; Triptorelin Pamoate

It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase, so we investigated the luteal phase after GnRHa triggering, supported with conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with low-dose hCG, induced a shorter luteal phase (11.2 ± 1.1 vs. 15.0 ± 1.6 days) and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG differentially affected corpus luteum function, ovarian size, free fluid accumulation, and patient comfort.

Topics: Adult; Chorionic Gonadotropin; Comprehension; Dose-Response Relationship, Drug; Drug Combinations; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Reproductive Techniques, Assisted; Triptorelin Pamoate

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

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

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus of 0.2 mg of triptorelin and Group II received 250 microg of recombinant HCG. No differences were observed in the number of oocytes retrieved or in the proportion of metaphase II oocytes between the groups. The OHSS rate was higher in donors that received recombinant HCG ( P = 0.003). Moreover, there was no significant difference between IVF parameters and outcome in the two groups. In conclusion, a GnRH agonist effectively triggers the final oocyte maturation in oocyte donors without negatively affecting implantation, pregnancy or miscarriage rates. Moreover, this regime effectively eliminates the risk of OHSS in this group of women.

Topics: Adolescent; Adult; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Recombinant Proteins; Treatment Outcome; Triptorelin Pamoate

The use of GnRH agonists instead of hCG to trigger ovulation seems to be an effective way to prevent subsequent hCG induced ovarian hyperstimulation in cases of polyfollicular development. But conflicting results are reported on the efficiency of subsequent luteal support using hCG and/or progesterone supplementation.. We investigated the efficiency and safety of different luteal support regimes in low dose gonadotropin stimulation non-ivf cycles. A risk for an imminent ovarian hyperstimulation was assumed if preovulatory estradiol levels rose up higher than 700 pg/ml and more than 12 intermediate sized follicles (8-14 mm) were observed. Thirty-six women received 0.5mg Triptorelin subcutaneously to trigger the ovulation inducing LH surge. After randomization, luteal support regimes started on day 2 after the Triptorelin administration with injections every second day five times in all. Group (a) received 5 x 1000 IU hCG, group (b) received 5 x 500 IU hCG, and group (c) received 5 x 250 mg progesterone, intramuscularly. The monitoring of the ovulation period and the subsequent luteal phase included sonographic measurement of ovarian diameter and estimation of LH, FSH, estradiol and progesterone levels 10 and 34 h as well as 8 days after Triptorelin administration.. We could prove ovulation in all women and did not find symptoms of ovarian hyperstimulation in any case. Midluteal controls showed extremely low gonadotropins in all groups indicating a long lasting pituitary down regulation after one injection of 0.5 mg Triptorelin. We found high normal sex steroid levels in both hCG groups. The progesterone group displayed a marked luteal phase defect with low levels of progesterone and estradiol in all cases.. The use of GnRH agonist in cases of polyfollicular development is capable to induce ovulation without a subsequent ovarian enlargement and/or any sign of hyperstimulation syndrome. Luteal support by low dose hCG does not counteract the benefit of GnRH agonist in preventing an ovarian hyperstimulation syndrome, but seems to remedy at least in part the possible deleterious effects of GnRH agonists on luteal functionality.

Topics: Adult; Chorionic Gonadotropin; Drug Administration Schedule; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Progesterone; Triptorelin Pamoate

We aimed to examine the serum levels of inhibin A, vascular endothelial growth factor (VEGF), tumour necrosis factor alpha (TNFalpha), estradiol (E2) and progesterone levels after triggering of final oocyte maturation with GnRH agonist compared with HCG in patients with polycystic ovaries (PCO) and to investigate the relationship between these markers and ovarian hyperstimulation syndrome (OHSS).. Twenty-eight patients with PCO, undergoing controlled ovarian hyperstimulation with FSH and GnRH antagonist for IVF-embryo transfer treatment, were randomized for triggering of final oocyte maturation with GnRH agonist (GnRH agonist group, n = 15) or HCG (HCG group, n = 13). Blood samples were obtained on the day of randomization and thereafter every 2-7 days. Serum levels of inhibin A, VEGF, TNFalpha, E2 and progesterone, the incidence of OHSS, ovarian size and pelvic fluid accumulation were evaluated.. Serum inhibin A, E2 and progesterone levels were significantly lower in the GnRH agonist group compared with the HCG group, particularly on the day of embryo transfer (P < 0.0001). Serum VEGF and TNFalpha levels were similar between the two groups. Four patients in the HCG group developed severe OHSS, whereas no patient had any symptoms or signs of OHSS in the GnRH-agonist group (P < 0.05).. In patients with PCO treated with FSH/GnRH antagonist, final oocyte maturation with GnRH agonist instead of HCG reduces significantly inhibin A, E2 and progesterone levels during the luteal phase. This phenomenon reflects the inhibition of the corpus luteum function and may explain, at least in part, the mechanism of OHSS prevention in high-risk patients. Our results do not support a crucial role for VEGF or TNFalpha in OHSS.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Inhibins; Oocytes; Ovarian Hyperstimulation Syndrome; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Triptorelin Pamoate; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

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

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

This multicentre, randomized study was performed to assess the efficacy and safety of 0.25 mg ganirelix (Orgalutran, Antagon) treatment, using triptorelin (Decapeptyl) in a long protocol as a reference treatment. In total, 236 subjects were randomized to treatment with ganirelix (0.25 mg, s.c.) and 119 to triptorelin (0.1 mg, s.c.) treatment (treatment ratio 2:1). Treatment with ganirelix started on day 6 of stimulation, whereas treatment with triptorelin started on menstrual cycle day 21 to 24 of the previous cycle (i.e. the midluteal phase). The ganirelix regimen was on average 17 days shorter (9 versus 26 days) compared to the triptorelin regimen. The median total dose of recombinant FSH (Puregon) used was 450 IU less (1350 versus 1800 IU) in the ganirelix protocol. The initial follicular growth was faster and, consequently, oestradiol concentrations were higher in the ganirelix group. On the day of human chorionic gonadotrophin (HCG), the mean number of follicles > or = 11 mm was 10.1 and 10.7 and the median serum oestradiol concentration was 1090 and 1370 pg/ml in the ganirelix and triptorelin groups respectively. Per attempt, 7.9 and 9.6 oocytes (mean) were retrieved in the ganirelix and triptorelin groups respectively. The fertilization rates (64.0% ganirelix and 64.9% triptorelin) and the mean number of good quality embryos (2.7 and 2.9) were comparable in both treatment groups. The implantation rate was identical (22.9%). The ongoing pregnancy rate per attempt was 31.0 and 33.9% in the ganirelix and triptorelin groups respectively. The ganirelix regimen showed an improved local tolerance in that the percentage of subjects with at least one local skin reaction was 2-fold lower than in the triptorelin group (11.9 versus 24.1%). Taking all data together, it may be concluded that ganirelix offers a new treatment regimen in ovarian stimulation that is short, safe and well-tolerated, optimizing convenience for the patient.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Embryo Transfer; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteinizing Hormone; Luteolytic Agents; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Treatment Outcome; Triptorelin Pamoate

The clinical outcome of intrauterine insemination (IUI) treatment cycles employing a gonadotrophin-releasing hormone agonist [GnRHa, triptorelin (Decapeptyl)] or human chorionic gonadotrophin (HCG) for ovulation induction was compared. A group of 48 patients presenting with amenorrhoea, oligomenorrhoea or unexplained infertility were all treated with human menopausal gonadotrophins (HMG) from day 5 of the cycle, on an individualized schedule. They were then randomly divided into two groups to receive either a single s.c. injection of 0.1 mg triptorelin or a single i.m. injection of 10,000 IU HCG after follicular maturation. IUI was performed approximately 24 and 48 h following the injection. A transitory increase in serum luteinizing hormone and follicle stimulating hormone concentrations was achieved following injection of GnRHa. A total of 24 patients received 72 treatment cycles with GnRHa, producing 11 conceptions (15.3%) and two abortions (18.2%), resulting in a term pregnancy rate of 13.6%. There were four cases of grade 3-4 ovarian hyperstimulation syndrome (OHSS), two of which were conception cycles. In all, 24 patients underwent 68 cycles treated with HCG, producing 18 conceptions (26.5%) and six abortions (33.3%), resulting in a term pregnancy rate of 19.0%. There were eight cycles of grade 3-4 OHSS, two of which were conception cycles. These results show that an s.c. injection of a relatively low dose of GnRHa can be as effective as HCG in producing pregnancy in IUI treatment cycles.

Topics: Abortion, Spontaneous; Chorionic Gonadotropin; Estradiol; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Insemination, Artificial, Homologous; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Triptorelin Pamoate; Twins

In a prospective, controlled, randomized study where two different agonists were used, we compared three different long desensitization protocols for induction of multiple follicular growth in medically assisted conception cycles. In protocol A, 30 patients were injected with buserelin twice a day for 15 days prior to ovarian stimulation until human chorionic gonadotrophin (HCG) administration. In protocol B, 30 patients were injected with a single dose of long acting Triptorelin (3.75 mg) 15 days before the ovarian stimulation onset. In protocol C, 30 patients were injected with the long acting Triptorelin 4 weeks before ovarian stimulation followed by daily administration of 0.1 mg of the same agonist until HCG injection. There was no difference in the ovarian response to exogenous gonadotrophin stimulation, except for the presence of premature luteinization in two patients in group B. A significantly higher number of mature oocytes was collected from patients with protocol A; however, the fertilization and cleavage rate demonstrated no significant difference among the three groups of patients. The ongoing pregnancy rate and the implantation rate per treatment cycle were very similar in the three study groups. When the convenience, cost and side-effects for the patient are being considered, protocol B should be selected as the first choice when the agonist is utilized for the purpose of inducing pituitary desensitization before and during ovarian stimulation.

Topics: Adult; Buserelin; Delayed-Action Preparations; Down-Regulation; Drug Administration Schedule; Embryonic and Fetal Development; Female; Fertilization in Vitro; Hormones; Humans; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Prospective Studies; Time Factors; Triptorelin Pamoate

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

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

Patients aged ≥35 years and DOR undergoing their first IVF/ICSI cycle were enrolled in this retrospective cohort study: 139 and 600 patients underwent the PPOS and mild stimulation protocols, respectively. The primary outcomes were cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR). The secondary outcomes were the number of oocytes retrieved and top-quality embryos.. There was nearly no significant difference of baseline characteristics between the two groups. Although a greater amount of total gonadotropin (1906.61 ± 631.04 IU vs. 997.72 ± 705.73 IU,. The PPOS protocol is an effective alternative to the mild stimulation protocol for advanced age patients with DOR, as it provides comparable reproductive outcomes and better control of premature LH surge. Further, more oocytes and top-quality embryos were obtained in the PPOS group, which had a positive association with conservative CCPR and CLBR.

Topics: Adult; Chorionic Gonadotropin; Clomiphene; Cohort Studies; Dydrogesterone; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Letrozole; Live Birth; Maternal Age; Medroxyprogesterone Acetate; Menotropins; Odds Ratio; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovarian Reserve; Ovulation Induction; Pregnancy; Pregnancy Rate; Progestins; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

Aim of this report is to alert clinicians about the potential significant sequelae of administering depot gonadotropin-releasing hormone agonists (GnRHa) shortly after oocytes cryopreservation. In our case report, a 28-year-old nulligravid Caucasian woman diagnosed with breast cancer underwent controlled ovarian stimulation-oocyte cryopreservation before chemotherapy. The oocyte retrieval was performed without complications and the woman was discharged after five hours. Three days later, the patient self-injected depot-GnRHa as chemoprotective agent, as indicated by the oncologist. The next day, the patient referred to the emergency room and she was diagnosed with ovarian hyperstimulation syndrome (OHSS) and required inpatient care. As a consequence, the start of the chemotherapy was delayed by two weeks. In conclusion, chemoprotection with depot-GnRHa after oocyte/embryo cryopreservation is not exempt from risks. The timing for depot-GnRHa administration should be established by the agreement between oncologist and gynecologist in order to avoid the risk of OHSS.

Topics: Adult; Anticoagulants; Antineoplastic Agents, Hormonal; Ascites; Cryopreservation; Cryoprotective Agents; Drug Administration Schedule; Enoxaparin; Female; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Letrozole; Oocyte Retrieval; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Recombinant Proteins; Self Administration; Triple Negative Breast Neoplasms; Triptorelin Pamoate

Are oocyte maturation rates different among 0.1, 0.2 and 0.4 mg triptorelin used for triggering final oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS) undergoing ICSI?. A dose of 0.1 mg triptorelin results in similar oocyte maturation rates compared to higher doses of 0.2 and 0.4 mg in patients at high risk for OHSS undergoing ICSI.. The GnRH agonist triptorelin is widely used instead of hCG for triggering final oocyte maturation, in order to eliminate the risk of severe OHSS in patients undergoing ovarian stimulation for IVF/ICSI. However, limited data are currently available regarding its optimal dose use for this purpose in patients at high risk for OHSS.. A retrospective study was performed between November 2015 and July 2017 in 131 infertile patients at high risk for severe OHSS undergoing ovarian stimulation for ICSI. High risk for severe OHSS was defined as the presence of at least 19 follicles ≥11 mm in diameter on the day of triggering final oocyte maturation.. Ovarian stimulation was performed with recombinant FSH and GnRH antagonists. Patients received 0.1 (n = 42), 0.2 (n = 46) or 0.4 mg (n = 43) triptorelin for triggering final oocyte maturation. Hormonal evaluation of FSH, LH, estradiol (E2) and progesterone (PRG) was carried out on the day of triggering final oocyte maturation, 8 and 36 hours post triggering and 3, 5, 7, and 10 days after triptorelin administration. During this period, all patients were assessed for symptoms and signs indicative of severe OHSS development. Primary outcome measure was oocyte maturation rate, defined as the number of metaphase II (MII) oocytes divided by the number of cumulus-oocyte-complexes retrieved per patient. Results are expressed as median (interquartile range).. No significant differences in patient baseline characteristics were observed among the 0.1 mg, the 0.2 mg and the 0.4 mg groups. Regarding the primary outcome measure, no differences were observed in oocyte maturation rate among the three groups compared [82.6% (17.8%) versus 83.3% (18.8%) versus 85.1% (17.2%), respectively, P = 0.686].In addition, no significant differences were present among the 0.1 mg, 0.2 mg and 0.4 mg groups, regarding the number of mature (MII) oocytes [21 (13) versus 20 (6) versus 20 (11), respectively; P = 0.582], the number of oocytes retrieved [25.5 (13) versus 24.5 (11) versus 23 (12), respectively; P = 0.452], oocyte retrieval rate [81.0% (17.7%) versus 76.5% (23.5%) versus 75.0% (22.5), respectively; P = 0.088], the number of fertilized (two pronuclei) oocytes [12.5 (9) versus 14.5 (7) versus 14.0 (8), respectively; P = 0.985], fertilization rate [71.7% (22%) versus 77.1% (19.1%) versus 76.6% (23.3%), respectively; P = 0.525] and duration of luteal phase [7 (1) versus 8 (2) versus 7 (1) days, respectively; P = 0.632]. Moreover, no significant differences were present among the three triptorelin groups regarding serum levels of LH, FSH, E2 and PRG at any of the time points assessed following triggering of final oocyte maturation.. This is a retrospective study, and although there were no differences in the baseline characteristics of the three groups compared, the presence of bias cannot be excluded.. Based on the results of the current study, it appears that triggering final oocyte maturation with a lower (0.1 mg) or a higher dose (0.4 mg) of triptorelin, as compared to the most commonly used dose of 0.2 mg, does not confer any benefit in terms of oocyte maturation rate in patients at high risk for severe OHSS.. No external funding was obtained for this study. There are no conflicts of interest.

Topics: Adult; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follow-Up Studies; Humans; In Vitro Oocyte Maturation Techniques; Luteinizing Hormone; Oocytes; Oogenesis; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Retrospective Studies; Risk; Triptorelin Pamoate; Young Adult

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

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

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

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

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

Ovarian stimulation in IVF cycle results in luteal supraphysiological steroid concentrations especially for high response patients. The aim of this study was to evaluate the efficacy of ovarian steroid hormone suppression in luteal phase after oocyte retrieval for preventing severe ovarian hyperstimulation syndrome (OHSS) in high-risk patients with embryo cryopreservation.. 281 patients with high risk of OHSS were enrolled in this study among 4735 infertile women undergoing their first IVF treatment. The subjects were allocated into treatment and control group. The treatment group (n = 161) received letrozole (n = 43), mifepristone (n = 51), cetrotide (n = 39) and three-drug combinations (n = 28) during the luteal phase after oocyte retrieval, respectively. The control group (n = 120) received no medicine. Fertilization rate, good embryo rate, serum steroid concentration, clinical outcome, and incidence of severe OHSS were compared between the two groups.. On days 2, 5 and 8 after oocyte retrieval, serum estradiol levels in the letrozole and three-drug combination therapy group were significantly lower than in the other three groups at the same time (P < 0.001, respectively). There were no significantly difference of serum luteinizing hormone concentration on days 2, 5 and 8 and progesterone concentration on day 8 after oocyte retrieval among the five groups (P > 0.05, respectively). Compared with the control group, the incidence of severe OHSS, the paracentesis rate, the duration of hospitalization and the days of luteal phase in each subgroup of treatment groups was not significantly decreased (P > 0.05, respectively).. Our findings indicate that steroidal ovarian suppression in luteal phase after oocyte retrieval seems to be unable to prevent severe OHSS in high-risk patients with embryo cryopreservation.

Topics: Adult; Case-Control Studies; Chorionic Gonadotropin; Down-Regulation; Drug Therapy, Combination; Estradiol; Female; Fertilization in Vitro; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Injections, Intramuscular; Luteal Phase; Luteinizing Hormone; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Treatment Outcome; Triptorelin Pamoate

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

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

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

Topics: Adult; Case-Control Studies; Chorionic Gonadotropin; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Hormones; Humans; Infertility, Female; Luteal Phase; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Progesterone; Progestins; Reproductive Control Agents; Risk; Triptorelin Pamoate

In an attempt to evaluate the effectiveness of a novel modified ultra-long agonist (ULA) protocol on polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI), a retrospective study of 499 women employed with either ULA or conventional long agonist (LA) protocol was analyzed. In high BMI group (>25 kg/m²), the ULA protocol yielded significant higher clinic pregnancy rate (PR) (70.2% versus 50.8%, p < 0.05), implantation rate (52.7% versus 35.7%, p < 0.05) and live birth rate (63.8% versus 39.0%, p < 0.05) when compared with LA protocol. In low BMI group (≤25 kg/m²), the ULA protocol also demonstrated a higher clinic PR (70.8% versus 59.5%, p < 0.05) whereas implantation rate and live birth rate are comparable. Within ULA protocol, the clinic PR, implantation rate and live birth rate are similar between high and low BMI patients. Similarly, the clinic PR and live birth rate demonstrated no significant difference within LA group but there is a significant lower implantation rate (35.7% versus 63.9%, p < 0.05) observed in high BMI patients. No difference in miscarriage rate and severe OHSS rate was found among all groups. In conclusion, ULA protocol benefits the IVF outcomes of PCOS patients with high BMI status.

Topics: Adult; Birth Rate; Body Mass Index; China; Drug Administration Schedule; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Overweight; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Maintenance; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

To investigate the mRNA expression of genes related to steroidogenesis and OHSS in granulosa cells (GCs) of patients triggered with GnRH agonist compared to patients triggered with hCG.. Mural GCs were obtained at the time of oocyte retrieval and gene expression was analyzed using quantitative real time RT-PCR.. Single center, case control study.. 24 women who were treated with GnRH agonist or hCG for triggering of ovulation.. GC collection.. The expression of genes related to steroidogenesis and OHSS in mural GCs.. The fertilization rate was similar in the two groups. The mRNA expression of CYP19A1 (0.50 vs 1, arbitrary unit), CYP11A1 (0.6 vs. 1) and 3 beta hydroxysteroid-dehydrogenase (0.39 vs 1) was significantly lower in the GnRH group. The expression of VEGF (0.74 vs. 1) and inhibin β B (0.38 vs 1) was lower in the GnRH analog triggered group.. Expression of genes related to steroidogenesis is lower at the time of oocyte retrieval in patients triggered with GnRH agonist. The decreased expression of VEGF and inhibin β B in the GnRH agonist group can explain the mechanism of early OHSS prevention.

Topics: 3-Hydroxysteroid Dehydrogenases; Adult; Aromatase; Case-Control Studies; Cholesterol Side-Chain Cleavage Enzyme; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gene Expression; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Inhibins; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Phosphoproteins; Receptors, LH; Reverse Transcriptase Polymerase Chain Reaction; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

Controlled ovarian hyperstimulation (COH) which combining GnRH antagonist co-treatment and GnRH agonist trigger with an additional 1500 IU hCG luteal rescue on day of oocytes retrieval, has become a common tool aiming to reduce severe ovarian hyperstimulation syndrome (OHSS). In the present, proof of concept study, we evaluate whether by deferring the hCG rescue bolus for 3 days, we are still able to rescue the luteal phase.. Patients undergoing the GnRH-antagonist protocol, who were considered at high risk for developing severe OHSS and received GnRH-agonist for final oocyte maturation, were included. For luteal phase support, all patients received an "intense" luteal support. Those who had no signs of early moderate OHSS on day 3 after oocytes retrieval were instructed to inject 1500 IU of HCG bolus (hCG group). Ovarian stimulation characteristics and mid luteal progesterone levels were compared between those who received the HCG bolus and those who did not.. Eleven IVF cycles were evaluated, 5 in the hCG group and 6 in the intense luteal support only group. While no in-between group differences were observed in ovarian stimulation characteristics, significantly higher mid luteal progesterone levels (>127 nmol/L vs 42.1 ± 14.5 nmol/L, respectively) and a non-significant increase in pregnancy rate (40% vs 16.6%, respectively), were observed in those who receive the hCG bolus compared to those who did not.. hCG luteal rescue should be offered 3 days after oocytes retrieval only to those patients with no signs of early moderate OHSS. Further studies are required to elucidate the appropriate regimen of luteal HCG administration in patients undergoing final follicular maturation with GnRH-agonist.

Topics: Adult; Biomarkers; Chorionic Gonadotropin; Drug Administration Schedule; Drug Therapy, Combination; Embryo Transfer; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Luteal Phase; Oocyte Retrieval; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Time Factors; Treatment Outcome; Triptorelin Pamoate

Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol?. Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol.. Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk.. This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers.. There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria.. Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10-14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not.. The small number of women with severe early OHSS may have prevented identification of other significant risk factors.. Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10-14 mm diameters even with few larger follicles.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Cohort Studies; Corpus Luteum; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Quebec; Retrospective Studies; Risk Factors; Severity of Illness Index; Triptorelin Pamoate; Turkey; Ultrasonography

To compare the serum and follicular fluid (FF) concentrations of stem cell factor (SCF) as well as the serum urocortin 1 (UCN1) concentration in gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) protocols for controlled ovarian hyperstimulation (COH) in IVF patients.. Follicular fluids and blood samples of 42 infertile women undergoing COH for IVF-embryo transfer with either GnRH agonist (n = 22) or GnRH antagonist (n = 20) protocols from 2010 to 2011 were collected during oocyte retrieval. SCF concentrations of serum and FF were assessed by sandwich enzyme immunoassay using ELISA Kit for SCF kid. Serum UCN1 concentration were measured using commercially available enzyme-linked immunosorbent assay.. Concentrations of serum UCN1, serum and FF SCF were similar in the two groups. The serum SCF levels correlated strongly with the follicular SCF levels (r = 0.770, p < 0.001). The mean implantation rate, biochemical and clinical pregnancy rate and live birth rate per cycle were also similar in the groups.. These observations suggest that there is no significant difference in follicular microenvironment in terms of SCF and UCN1 between agonist and antagonist protocols.

Topics: Adult; Embryo Implantation; Embryo Transfer; Enzyme-Linked Immunosorbent Assay; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Hormones; Humans; Infertility, Female; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Stem Cell Factor; Triptorelin Pamoate; Urocortins

To evaluate the efficacy and safety of ovulation triggering by agonists in antagonists IVF cycles with fresh embryo transfer in modulating low HCG dose for luteal phase support in patients at risk of ovarian hyperstimulation syndrome (OHSS).. In an observational study from September 2011 to March 2013, we triggered with agonist 107 cycles with OHSS risk, we initially triggered 39 cycles with 2 doses of Triptorelin 0.1 mg. Injection of 1500 IU HCG was performed one hour after the pick up and a second injection of 1500 IU was made 5 days later (group 1) combined with 400 mg of natural progesterone vaginally. In the following 68 cycles we removed the second HCG injection and increased to 600 mg vaginal progesterone associated with E2 4 mg orally (group 2).. Group 1: the ongoing pregnancy rate and birth rate in fresh cycle is respectively 37.1% and 34.3% and the cumulative ongoing pregnancy rate and birth rate per patient is 43.6% and 41%. We recorded three late onset OHSS in pregnant women. Group 2: ongoing pregnancy rate in fresh cycle is 39.6%, the current cumulative ongoing pregnancy rate per patient was 45.6%. We observed a case of early onset OHSS.. Triggering with agonist and administering an injection of 1500 IU of HCG the day of the pick up appears to be effective in women at risk of OHSS. The exclusion of all OHSS is still not reached. The search for the best protocol and its indications should continue.

Topics: Administration, Intravaginal; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Risk Factors; Triptorelin Pamoate

To evaluate, whether Gonadotropin-releasing hormone-agonist (GnRH-agonist or GnRH-ag) trigger in patients undergoing the ultrashort GnRH-ag/GnRH-antagonist (GnRH-ant) protocol is as effective as in patients at high risk to develop severe ovarian hyperstimulation syndrome (OHSS), who undergo the multidose GnRH-ant protocol.. Cohort study.. University hospital.. All consecutive women aged ≤35 years admitted to our IVF unit from January 2011 to October 2011 who reached the ovum pick-up stage.. Triggering final oocytes maturation by GnRH-ag instead of hCG, in high-responder patients undergoing either the ultrashort GnRH-ag/GnRH-ant or the multidose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocols.. Ovarian stimulation characteristics, percentage of mature oocytes, fertilization and pregnancy rates.. No inbetween groups differences were observed in ovarian-stimulation related variable, percentage of mature oocytes, fertilization or pregnancy rates. No case of moderate-severe OHSS was reported in the study, or the control groups.. Three consecutive doses of daily GnRH-ag administration at the beginning of ultrashort flare GnRH-ag/GnRH-ant COH protocol, did not interfere with the ability of the GnRH-ag to trigger final oocytes maturation at the end of the COH cycle.

Topics: Adult; Cohort Studies; Databases, Factual; Female; Fertilization; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Luteolytic Agents; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Risk Factors; Triptorelin Pamoate

To evaluate the reproductive performance and safety of gonadotropin-stimulated intrauterine insemination (IUI) cycles in women at risk for ovarian hyperstimulation syndrome (OHSS) when final follicle maturation was induced using a gonadotropin-releasing hormone (GnRH) agonist.. Thirty-three women presenting with a history of cancelled ovarian stimulation for fear of OHSS, underwent repeat gonadotropin ovarian stimulation for IUI. They were all found to be at high-risk for OHSS once more, and were counseled to receive a GnRH agonist to trigger final follicle maturation before insemination. GnRH agonist trigger of ovulation (triptorelin) was given subcutaneously every 12 hours in three repeated doses: 0.3, 0.2, 0.2 mg, respectively.. Induction with the agonist was associated with a 30.3% take-home pregnancy rate and 20% miscarriage rate. Multiple pregnancy rates were 26.7%. There were no reported cases of clinically significant moderate/severe ovarian hyperstimulation syndrome.. The use of a GnRH agonist to trigger final follicle maturation in stimulated cycles of hyper responders was associated with a favorable reproductive outcome and no incidence of OHSS. The rate of multiple pregnancies nevertheless was found to be uncontrollably elevated, raising serious concerns regarding the safety of this protocol in standard clinical practice in the context of IUI.

Topics: Adult; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Insemination, Artificial; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy, Multiple; Triptorelin Pamoate

Follicular growth, ovulation, and luteinization are influenced by interactions of peptide and steroid hormone-signaling cascades in the ovary. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the regulation of several endocrine processes and is present in ovarian follicular fluid (FF). However, little is known about PACAP in FF with regard to maturation, ovulation, fertilization, and successful pregnancy. The aim of this pilot study was to investigate whether there is a correlation between PACAP concentration in FF and ovarian response to superovulation treatment in infertile women, performed in volunteers (n = 132; aged between 20 and 35). After treatment, the number of harvested oocytes was recorded and PACAP immunoreactivity in FF was measured by radioimmunoassay. All the corresponding PACAP concentrations were below 290 fmol/ml in cases when the number of harvested oocytes exceeded 14 per patient, while in all cases above 290 fmol/ml, the number of oocytes was below 14. Using these cutoff values, we determined three study groups: high-PACAP concentration, high-oocyte number, and low-PACAP concentration-low-oocyte number groups. Median values of PACAP concentration in these groups were 411.2, 106.5, and 101.0 fmol/ml, respectively, while the median values of harvested oocytes were 5.5, 19.0, and 5.0, respectively. Differences were significant, indicating a correlation between concentration of PACAP in FF and the number of recruited oocytes. Higher concentrations of PACAP in FF might be associated with lower number of developing oocytes, while low concentrations of PACAP might correlate with a markedly higher number of ova retrieved, thus predicting a higher chance for ovarian hyperstimulation. Our present study is among the first few human clinical studies with direct conclusions drawn for possible clinical impact of PACAP.

Topics: Adult; Biomarkers; Cell Count; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone, Human; Follicular Fluid; Humans; Infertility, Female; Oocytes; Ovarian Hyperstimulation Syndrome; Ovary; Pilot Projects; Pituitary Adenylate Cyclase-Activating Polypeptide; Recombinant Proteins; Superovulation; Tissue and Organ Harvesting; Triptorelin Pamoate; Young Adult

This study evaluated the differentially modulated expression of vascular mediators in oocyte donors after hCG vs. GnRHa triggering, trying to understand ovarian hyperstimulation syndrome pathophysiology. Donors who received GnRH agonist triggering showed a statistically significant decrease in vascular endothelial growth factor in follicular fluid and in mRNA expression in granulosa cells, with no differences in angiopoietin 2 and vascular endothelial cadherin levels in serum or follicular fluid. This differential regulation of vascular endothelial growth factor by hCG might explain the higher likelihood of ovarian hyperstimulation syndrome following hCG administration compared with GnRH agonists.

Topics: Angiopoietin-2; Antigens, CD; Cadherins; Chorionic Gonadotropin; Enzyme-Linked Immunosorbent Assay; Female; Fertility Agents, Female; Follicular Fluid; Gonadotropin-Releasing Hormone; Granulosa Cells; Humans; Oocyte Donation; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spain; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

To compare clinical and embryological characteristics in donor cycles triggered for final oocytes maturation with Pregnyl 10 000 IU i.m. versus triptorelin 0.2 mg s.c. in the same patients in two sequential stimulation cycles. The aim of the study is to decrease the risk of the development of ovarian hyperstimulation syndrome (OHSS) at high response donors by the replacement of Pregnyl 10 000 IU i.m. vs. triptorelin 0.2 mg s.c. The administration of a single dose of gonadotropin-releasing hormone agonist (triptorelin 0.2 mg s.c.) induces release of LH from the pituitary gland similarly to a spontaneous LH surge.. Prospective cross-over trial.. Sanatorium Pronatal, Praha.. From August 2009 to July 2010 we analysed 24 stimulation cycles in 12 egg donors treated with GnRH antagonist protocol with recombinant FSH (follitropin beta). We identified patients with more than 15 follicles during examination by transvaginal ultrasound. When at least 3 leading follicles reached 17 mm in diameter we administrated Pregnyl 10 000 IU i.m. for final oocytes maturation and triptorelin 0.2 mg s.c in the subsequent treatment cycle.. The primary outcome measure was number of oocytes, proportion mature oocytes and fertilized oocytes. The secondary outcome were duration of FSH stimulation, total dose of gonadotropins and mean daily dose of gonadotropins. Data was analysed by paired t-test. We retrieved 17.2 +/- 8.6 vs. 15.8 +/- 5.3 (ns) oocytes, 12.6 +/- 7.3 vs. 13.0 +/- 5.4 (ns) metaphase II oocytes, proportion of metaphase II oocytes (%) was 73 vs. 83 (ns), number of fertilized oocytes 11.5 +/- 6.7 vs. 11.7 +/- 4.5 (ns), fertilization rate (%) 91 vs. 90 (ns) in Pregnyl's vs. triptorelin's group, resp. Duration of FSH stimulation (days) 12.2 +/- 0.8 vs. 12.4 +/- 0.7 (ns), total dose of gonadotropins (IU) 1744 +/- 277 vs. 1740 +/- 276 (ns), mean daily dose of gonadotropins (IU) 238 +/- 43 vs. 221 +/- 36 (ns), were not statistically different in both groups.. Number of mature oocytes and subsequent embryonic cleavage is comparable to standard hCG treatment. There are no differences in clinical and embryological characteristics in both groups. Only one patient with administration of Pregnyl 10 000 IU i.m. was treated for OHSS grade II by vaginal paracentesis. Administration of triptorelin 0.2 mg s.c. is a safe and effective approach to achieve mature oocytes in egg donation programme, where we do not take care of implantation, which has got some limitations based on several studies.

Topics: Chorionic Gonadotropin; Female; Humans; Oocyte Donation; Oocytes; Ovarian Hyperstimulation Syndrome; Triptorelin Pamoate

Topics: Female; Freezing; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Pregnancy; Triptorelin Pamoate

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.

Topics: Adult; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Oocyte Donation; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Triptorelin Pamoate

Herein we report a case of ovarian hyperresponse after luteal phase GnRH-agonist administration in a woman planning to undergo ovarian stimulation for IVF in a long GnRH-agonist protocol.. A normogonadotropic 25-year-old woman undergoing ICSI treatment for male factor infertility underwent three cycles of controlled ovarian stimulation, two in a GnRH-antagonist protocol, one in a long luteal GnRH-agonist protocol.. In the first GnRH-antagonist cycle, ovarian stimulation was performed with 150 IE recombinant FSH and 22 oocytes were retrieved. In the second GnRH-antagonist cycle using the same protocol, six oocytes were retrieved. The estradiol levels on the day of hCG administration were 3,692 and 3,209 pg/ml, respectively. In a third cycle, 3.75 mg triptorelin was administered in the luteal phase and the patient showed ovarian hyperresponse to the endogenous gonadotropin flare with estradiol levels of 19,102 pg/ml, abdominal distension and discomfort, and massive bilateral ovarian enlargement (total ovarian volume 268 cm(3)). Ovarian cysts persisted for 4 weeks and necessitated cyst aspiration before further treatment.. The flare-up effect of GnRH-agonist administration can, in rare cases, cause massive ovarian hyperresponse with associated health risks and significant postponement of treatment.

Topics: Female; Fertility Agents; Gonadotropin-Releasing Hormone; Humans; Infertility, Male; Luteal Phase; Male; Ovarian Hyperstimulation Syndrome; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate; Young Adult

We retrospectively studied 429 IVF donor cycles in which ovulation was triggered with either hCG (175 cycles) or GnRH agonist (254 cycles). Of the donors in whom ovulation was triggered with hCG, 3.2% developed symptoms of moderate (2.2%) or severe (1%) ovarian hyperstimulation syndrome, while none of the IVF donor cycles that were triggered with the GnRH agonist presented ovarian hyperstimulation syndrome, needed coasting, or were cancelled.

Topics: Adult; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteolytic Agents; Oocyte Donation; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Retrospective Studies; Treatment Failure; Triptorelin Pamoate

In a prospective cohort study, we compared the effect of hCG and GnRH agonist triggering of final oocyte maturation on vascular endothelial growth factor production. Vascular endothelial growth factor follicular fluid concentration was significantly lower in response to GnRH agonist versus hCG, which may partially explain the absence of OHSS in these of women.

Topics: Adolescent; Adult; Cell Differentiation; Chorionic Gonadotropin; Cohort Studies; Female; Fertilization in Vitro; Follicular Fluid; Gonadotropin-Releasing Hormone; Humans; Luteolysis; Oocyte Donation; Oocytes; Oogenesis; Ovarian Hyperstimulation Syndrome; Ovum; Prospective Studies; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate; Vascular Endothelial Growth Factor A; Young Adult

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

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

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

OHSS is a serious complication of COH and PCOS is a major risk factor for its development.. The objective of this study is to evaluate the effect of the application of GnRH-agonist in patients with PCOS for triggering the ovulation and prophylactic of OHSS.. In the present study we evaluated 29 patients with PCOS who had been stimulated for the purposes of ART with gonadotrophins and GnRH-antagonist and application of GnRH-agonist (Decapeptyl; Dipherilyn-0.2 mg) instead of HCG.. From the observed group one patient developed severe form of late OHSS. The average number of aspirated oocytes was 22.5 and the clinical pregnancy was 46.8%.. The application of protocole with GnRH-antagonist and triggering of the ovulation with GnRH-agonist is a good alternative when a high risk of development of OHSS exists and our results prove that.

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

A bolus dose of GnRH agonist can substitute for hCG as a trigger for the resumption of meiosis in ovarian stimulation with GnRH antagonists, which has been suggested to reduce the risk of ovarian hyperstimulation syndrome (OHSS). As the efficacy of this measure in fresh embryo transfer (ET) cycles is unclear, we evaluated a new clinical concept of GnRH-agonist triggering.. In this prospective, observational proof-of-concept study, 20 patients considered at increased risk of developing OHSS (> or = 20 follicles > or = 10 mm or estradiol > or = 4000 pg/ml, or a history of cycle cancellation due to OHSS risk or the development of severe OHSS in a previous cycle) after ovarian stimulation and concomitant GnRH-antagonist administration had final oocyte maturation triggered with 0.2 mg triptorelin s.c. All two pronucleate (2 PN) oocytes were cryopreserved by vitrification, and frozen-thawed ETs (FT-ETs) were performed in an artificial cycle. Main outcome measures were the cumulative ongoing pregnancy rate per patient and the ongoing pregnancy rate per first ET. Secondary outcomes included the incidence of moderate-to-severe OHSS.. Of the 20 patients triggered with GnRH agonist, 19 patients underwent 24 FT-ETs in the observational period. The cumulative ongoing pregnancy rate was 36.8% (95% confidence interval: 19.1-59.0%). The ongoing pregnancy rate per first FT-ET was 31.6% (15.4-54.0%). No cases of moderate or severe OHSS were observed.. The present study is the proof of the concept that GnRH-agonist triggering of final oocyte maturation in combination with elective cryopreservation of 2 PN oocytes offers OHSS risk patients a good chance of pregnancy achievement, while reducing the risk of moderate and severe OHSS.

Topics: Adult; Cryopreservation; Embryo Transfer; Female; Gonadotropin-Releasing Hormone; Humans; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pilot Projects; Pregnancy; Pregnancy Rate; Prospective Studies; Triptorelin Pamoate

The aim of this study is to report a large series of patients (n = 1223) at risk of developing ovarian hyperstimulation syndrome (OHSS) who underwent coasting.. Coasting started when the leading follicle reached 16 mm and continued until the estradiol (E2) level fell to 3000 pg/ml.. The E2 level at the start of coasting was (mean +/ SD) 6408 +/- 446 and it fell to 2755 +/- 650 on the day of HCG injection, after (mean +/- SD) 2.89 +/- 0.94 days. The results were analysed according to the duration of coasting (< or = 3 days, group I: n = 983; >3 days, group II: n = 240). The number of oocytes retrieved was (mean SD) 16.45 +/- 6.25 and 14.93 +/- 6.01 in groups I and II respectively (P < 0.05). The fertilization rates were 63 and 65% in groups I and II respectively (P > 0.05). The implantation and clinical pregnancy rates were 26 and 52% in group I compared to 18 and 36% in group II respectively (P < 0.05). Severe OHSS occurred in 16 cases, which represented 0.13% of all stimulated cycles, and 1.3% of patients who were at risk of developing OHSS.. Our protocol of coasting was an effective measure in the prevention of OHSS, without jeopardizing the ICSI outcome. Coasting for >3 days is associated with a moderate decrease in the pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Cohort Studies; Drug Therapy, Combination; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Pregnancy; Retrospective Studies; Risk; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

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

Topics: Antineoplastic Agents, Hormonal; Female; Humans; Leiomyoma; Middle Aged; Ovarian Hyperstimulation Syndrome; Pleural Effusion; Triptorelin Pamoate; Uterine Neoplasms

Coasting, or withholding gonadotrophin administration while maintaining gonadotrophin-releasing hormone analogue until oestradiol drops to a safe concentration, is an alternative approach to prevent ovarian hyperstimulation syndrome (OHSS) in high responder patients. However, the length of this procedure has not been precisely studied. This paper is a retrospective study of 132 patients who showed a high response (oestradiol > 4500 pg/ml and/or more than 20 follicles > 17 mm) to ovarian stimulation and were coasted due to their high risk of developing OHSS, and evaluated the impact of the duration of coasting on IVF cycle outcome. Additionally, serum LH and progesterone concentrations were studied to investigate whether premature luteinization was present in these cycles and whether it might be related to coasting duration. A significant decrease in implantation rate was found when coasting was required for more than 4 days, together with a trend towards a higher cancellation rate. Premature luteinization was significantly elevated in women undergoing coasting compared with control women (34 versus 15.6%, P < 0.05). In the majority of patients who showed premature luteinization, coasting lasted >/=3 days. To conclude, prolonged coasting may affect the endometrium, anticipating the implantation window. These data may explain why some women undergoing extended coasting show a lower implantation rate compared with controls.

Topics: Adult; Biopsy; Estradiol; Female; Fertilization in Vitro; Gonadotropins; Humans; Luteinization; Luteolytic Agents; Ovarian Hyperstimulation Syndrome; Progesterone; Retrospective Studies; Triptorelin Pamoate

Ovarian hyperstimulation after a single dose of gonadotropin-releasing hormone (GnRH) analog is a rare phenomenon. A case of ovarian hyperstimulation-like syndrome after sole administration of triptorelin (Decapeptyl 3.75 mg) is reported in a woman who had undergone surgery for an endometriotic cyst. After administration of the drug, abdominal pressure increased with nausea and diffuse pelvic pain. Ultrasound examination showed bilateral enlargement of the ovaries (right 74 x 62 mm, left 62 x 53 mm), more than 10 follicles ranging in diameter from 15-25 mm, proliferative endometrium 7 mm thick and fluid in the Douglas pouch up to 25 x 23 mm thick. Estradiol plasma level was in the normal range. The syndrome spontaneously resolved in the course of treatment and a spontaneous pregnancy occurred when the triptorelin effect disappeared.

Topics: Adult; CA-125 Antigen; Endometriosis; Female; Humans; Infertility, Female; Laparoscopy; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Pregnancy; Tomography, X-Ray Computed; Triptorelin Pamoate; Ultrasonography

Topics: Adult; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovary; Polycystic Ovary Syndrome; Triptorelin Pamoate

A new treatment option for patients undergoing ovarian stimulation is the gonadotrophin-releasing hormone (GnRH) antagonist protocol, with the possibility to trigger a mid-cycle LH surge using a single bolus of GnRH agonist, reducing the risk of developing ovarian hyperstimulation syndrome (OHSS) in high responders and the chance of cycle cancellation. This report describes the use of 0.2 mg triptorelin (Decapeptyl) to trigger ovulation in eight patients who underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH, Puregon) and concomitant treatment with the GnRH antagonist ganirelix (Orgalutran) for the prevention of premature LH surges. All patients were considered to have an increased risk for developing OHSS (at least 20 follicles > or =11 mm and/or serum oestradiol at least 3000 pg/ml). On the day of triggering the LH surge, the mean number of follicles > or =11 mm was 25.1 +/- 4.5 and the median serum oestradiol concentration was 3675 (range 2980-7670) pg/ml. After GnRH agonist injection, endogenous serum LH and FSH surges were observed with median peak values of 219 and 19 IU/l respectively, measured 4 h after injection. The mean number of oocytes obtained was 23.4 +/- 15.4, of which 83% were mature (metaphase II). None of the patients developed any signs or symptoms of OHSS. So far, four clinical pregnancies have been achieved from the embryos obtained during these cycles, including the first birth following this approach. It is concluded that GnRH agonist effectively triggers an endogenous LH surge for final oocyte maturation after ganirelix treatment in stimulated cycles. Our preliminary results suggest that this regimen may prove effective in triggering ovulation and could be said to prevent OHSS in high responders. The efficacy and safety of such new treatment regimen needs to be established in comparative randomized studies.

Topics: Adult; Embryo Transfer; Estradiol; Female; Follicle Stimulating Hormone; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Humans; Infertility, Male; Luteinizing Hormone; Male; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Recombinant Proteins; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

The present study evaluates the potential beneficial effect of co-treatment with LHRH-agonist in resolving premenopausal tamoxifen's induced supraphysiological serum 17beta estradiol levels and persistent ovarian cysts. Ultrasonographic and serum hormonal evaluations were performed before, during, and following three consecutive injections of long acting LHRH-agonist administered to 14 premenopausal breast cancer patients treated with tamoxifen, who had supraphysiological serum 17beta estradiol levels and simultaneous persistent ovarian cysts. Within 3 weeks of the first LHRH-agonist injection, all patients had menopausal serum estradiol levels. Ovarian cysts completely disappeared within 2 months following the first injection. Following the discontinuation of LHRH-agonist co-treatment, serum estradiol levels remained in physiological levels and the ovaries remained a normal size in 64.3% of the patients for 13.3 +/- 11.5 months. 28.6% of the patients had a gradual reappearance of high serum estradiol levels and of ovarian cysts, and were, therefore, treated with a second course of LHRH-agonist. Following the second course, serum estradiol levels remained in physiological levels and the ovaries remained a normal size for 8-15 months. It is concluded that short duration of co-treatment with long acting LHRH-agonist administered to premenopausal breast cancer patients treated with tamoxifen, successfully resolved the tamoxifen-induced supraphysiological serum 17beta estradiol levels and the ovarian cysts.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Evaluation; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Middle Aged; Ovarian Cysts; Ovarian Hyperstimulation Syndrome; Premenopause; Progesterone; Tamoxifen; Triptorelin Pamoate; Ultrasonography

The study aims to evaluate whether serum vascular endothelial growth factor (VEGF) levels, before treatment with gonadotropins, may be considered a predictive marker of moderate ovarian hyperstimulation syndrome (OHSS). At the University of Pisa hospital infertility unit we have retrospectively selected 10 patients who developed moderate forms of OHSS and 30 control patients who presented a normal response to ovarian stimulation among 400 women undergoing in vitro fertilization (IVF). Serum samples were collected before starting pFSH administration (150-300 IU/day). VEGF levels in serum were measured. No statistically significant difference was found between the serum VEGF levels of patients who developed moderate forms of OHSS and women without any symptoms of the syndrome. Further, serum VEGF concentrations were not significantly correlated with the age of the patients, the number of international units of FSH administered during the cycle of stimulation, the follicle and oocyte numbers counted on the day of the egg retrieval or estradiol levels detected on the same day. This study demonstrates that serum VEGF levels, before starting gonadotropin treatment, are not predictive of the subsequent development of moderate forms of ovarian hyperstimulation syndrome.

Topics: Adult; Endothelial Growth Factors; Estradiol; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropins; Humans; Immunoenzyme Techniques; Lymphokines; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Retrospective Studies; Statistics, Nonparametric; Triptorelin Pamoate; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

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

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

The case of an arterial aorto-subclavian thromboembolism associated with a moderate ovarian hyperstimulation syndrome (OHSS) and following ovulation induction for in-vitro fertilization in a young woman is reported. Because of the lack of response to systemic thrombolysis, a left postero-lateral thoracotomy was performed on day 8 after embryo transfer. A fibrinocruoric embolus situated at the junction of the left subclavian artery from the aorta was removed through a left subclavian arteriotomy. The distal axillary embolus was removed by a retrograde balloon catheter embolectomy. A moderate OHSS was observed. The ovarian stimulation and OHSS-related risks of thromboembolism are discussed. We conclude that, in the absence of risk factors, counselling about possible complications resulting from stimulation must be emphasized.

Topics: Adult; Aorta; Chorionic Gonadotropin; Female; Gonadotropin-Releasing Hormone; Humans; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Subclavian Artery; Thromboembolism; Triptorelin Pamoate

Gonadotrophin-releasing hormone analogue (GnRHa) has been suggested as an alternative to human chorionic gonadotrophin (HCG) for triggering ovulation, while preventing ovarian hyperstimulation syndrome (OHSS). Since a prospective, controlled study would be unethical at this point, we used a retrospective, case-self control approach to compare GnRHa with HCG in that context. A group of 16 in-vitro fertilization (IVF) patients who had severe OHSS in previous cycles, in which HCG was given to trigger ovulation, were studied in subsequent cycles in which GnRHa was used. Each GnRHa cycle (case) was compared to a previous HCG cycle that resulted in OHSS (self control). None of these subsequent cycles resulted in severe OHSS. The use of GnRHa did not affect the number of oocytes retrieved or their quality. Serum oestradiol concentrations on the day of ovulation triggering were significantly (P < 0.01) higher in the GnRHa cycles compared to HCG cycles. Exogenous progesterone and oestradiol were effective in maintaining relatively constant serum oestradiol and progesterone serum concentrations during the luteal phase. Pregnancy rate per cycle was similar in the two groups. In conclusion, the use of GnRHa to induce ovulation in IVF patients, who are at high risk for developing OHSS, effectively eliminates this risk without affecting other parameters of the stimulation cycle.

Topics: Case-Control Studies; Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Retrospective Studies; Triptorelin Pamoate

Ovarian hyperstimulation syndrome (OHSS) is a major risk in patients undergoing ovulation induction protocols. Withholding injection of human chorionic gonadotrophin (HCG) may prevent the development of OHSS, but can also result in failure to ovulate and conceive. We have used a gonadotrophin-releasing hormone agonist (GnRHa) as an alternative to HCG in women not undergoing in-vitro fertilization in an attempt to prevent OHSS. The study included 12 cycles in 12 women scheduled for ovulation induction with human menopausal gonadotrophin (HMG) who were at risk of developing OHSS (oestradiol > 3500 pg/ml, number of follicles > 20). GnRHa was injected to induce the pre-ovulatory, luteinizing hormone surge which triggers follicular maturation. Progesterone was administered for luteal support. Six pregnancies were achieved, and none of the 12 women developed OHSS. Since the pregnancy rate in this study was acceptable, we can recommend the use of GnRHa instead of HCG in any case at risk of developing OHSS.

Topics: Estradiol; Female; Follicular Phase; Humans; Luteinizing Hormone; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Risk Factors; Triptorelin Pamoate

Individually adapted gonadotropin dosage is more successful than standardized schemes for ovarian stimulation prior to in vitro fertilization and embryo transfer. Unfortunately, differences in ovarian response can not be predicted reliably. In order to develop predictive parameters for ovarian response the data from 99 cycles in 69 patients were analysed retrospectively. Before initiating ovarian stimulation for in vitro fertilization, an untreated menstrual cycle was examined using a commonly used endocrinological screening protocol. The ovaries were then stimulated with exogenous gonadotropins after previous suppression of endogenous gonadotropin secretion using a long-acting GnRH-analogue. The predictive value of this endocrinological screening protocol for ovarian response was evaluated. Ovarian response was defined as the logarithmically transformed ratio of the serum estradiol concentration at ovulation induction, divided by the number of ampoules of exogenous gonadotropins administered. Comparison of the various hormone characteristics with ovarian response led to identification of two distinct groups of patients showing reduced ovarian response: those with elevated serum levels of FSH on the third cycle day (> 9 units/l, P < 0.0001), and those with elevated serum levels of estradiol on the third cycle day (> 190 pmol/l, P < 0.02). Patients with high serum levels of TSH in the TRH test responded poorly to ovarian stimulation (P < 0.05), but also showed significantly higher serum concentrations of FSH (P < 0.01). No parameter correlated positively with ovarian response.

Topics: Adult; Cell Count; Delayed-Action Preparations; Female; Gonadotropins, Pituitary; Humans; Menstrual Cycle; Oocytes; Ovarian Hyperstimulation Syndrome; Pituitary Gland; Predictive Value of Tests; Retrospective Studies; Secretory Rate; Triptorelin Pamoate

To analyse the incidence and factors associated with the ovarian hyperstimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk.. Two hundred forty-one consecutive IVF/GIFT cycles from January to December 1989.. Specialist fertility unit, Manchester, UK.. Pituitary suppression was effected by a daily subcutaneous injection of buserelin (500 micrograms) beginning 7 days before the expected menses. The ovarian stimulation was with variable amounts of human menopausal gonadotrophin. Ovulation was induced with 10,000 i.u. human chorionic gonadotrophin (hCG). From January to May (period A), gametes/embryos were replaced and 2000 i.u. hCG given, irrespective of the serum oestradiol (E2) concentration. From June to December (period B), all the embryos from women with an E2 > 3500 pg/ml on the day of ovulatory trigger were electively cryopreserved.. Serum E2, features of moderate or severe OHS, clinical pregnancies.. The OHS occurred in 10/105 (9.5%) and 12/136 (8.8%) cycles in periods A and B, respectively. Fewer women (6% versus 60%, P < 0.05) who had their embryos cryopreserved developed severe OHS compared with women with an E2 > 3500 pg/ml who became pregnant after gamete/embryo transfer in period A. The main factors associated with the development of OHS were serum E2 concentrations > 3500 pg/ml, whether gamete/embryos were replaced and the additional hCG given, the occurrence of a pregnancy and the presence of polycystic ovary disease.. The elective cryopreservation of all embryos from women with high E2 levels reduced the severity, but not the incidence of symptomatic OHS.

Topics: Adult; Buserelin; Cryopreservation; Embryo, Mammalian; Estradiol; Female; Fertilization in Vitro; Gamete Intrafallopian Transfer; Gonadotropin-Releasing Hormone; Humans; Incidence; Infertility, Female; Middle Aged; Ovarian Hyperstimulation Syndrome; Pregnancy; Risk Factors; Triptorelin Pamoate

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