lhrh--ala(6)-gly(10)-ethylamide- and Ovarian-Hyperstimulation-Syndrome

Abnormal luteal function is a common issue in assisted reproduction techniques associated with ovarian stimulation probably due to low levels of LH in the middle and in the late luteal phase. This defect seems to be associated with supraphysiological steroid levels at the end of follicular phase. The luteal phase insufficiency has not got a diagnostic test which has proven reliable in a clinical setting. Luteal phase after ovarian stimulation becomes shorter and insufficient, resulting in lower pregnancy rates. Luteal phase support with progesterone or hCG improves pregnancy outcomes and no differences are found among different routes of administration. However, hCG increases the risk of ovarian hyperstimulation syndrome. In relation to the length of luteal support, the day of starting it remains controversial and it does not seem necessary to continue once a pregnancy has been established. After GnRHa triggering ovulation, intensive luteal support or hCG bolus can overcome the defect in luteal phase, but more studies are needed to show the LH utility as support.

Topics: Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone

Can the luteal phase support be improved in terms of efficacy, hormonal profiles and convenience as compared with today's standard care?. Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can replace the traditional used luteal phase support with exogenous progesterone.. A bolus of hCG for final maturation of follicles in connection with COS may induce the risk of OHSS and the luteal phase progesterone levels rise very abruptly in the early luteal phase.. This is a proof-of-concept study conducted as a three arm RCT with a total of 93 patients. First patient enrolled in January 2012 and the study finished in January 2014.. Normal responder women undergoing IVF/ICSI treatment in a university hospital. One arm served as control, where women followed a standard antagonist protocol. Two study arms were included both having 125 IU hCG daily for luteal phase support without exogenous progesterone after using a GnRHa trigger for ovulation induction. In both study arms exogenous FSH was stopped on stimulation day 6 and replaced by exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood samples were obtained on the day of ovulation induction, on the day of oocyte pickup (OPU) and day OPU + 7.. The mean serum levels of hCG did not exceeded the normal physiological range of LH activity in any samples. Mid-luteal progesterone levels were significantly higher in the two study groups receiving daily low-dose hCG for luteal phase support as compared with the control group (control group: 177 ± 27 nmol/l; study group 1: 334 ± 42 nmol/l; study group 2: 277 ± 27 nmol/l; (mean ± SEM). No differences in reproductive outcome were seen between groups.. The number of patients included is limited and conclusions need to be verified in a larger RCT.. Endogenous production of progesterone may become more attractive as the luteal phase support with levels of LH-like activity only in the physiological range and may, from the patients' point of view, replace inconvenient exogenous progesterone preparation. Further hCG may reduce the cost of stimulation and may collectively be used for stimulation of the follicular phase, ovulation induction and for luteal phase support.. An unrestricted grant from ARTS Biologics made this study possible. None of the authors has any competing interests to declare.. ClinicalTrial.gov number: NCT01504139.. 28 December 2011.

Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteal Phase; Oocytes; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Progesterone; Time Factors; Treatment Outcome

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocyte Retrieval; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate

To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes.. The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed.. A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles.. The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.

Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy

To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) <4,000 pg/mL at risk of ovarian hyperstimulation syndrome (OHSS).. Retrospective cohort study.. University-based tertiary-care fertility center.. Patients <40 years old with peak E(2) <4,000 pg/mL at risk of OHSS who underwent IVF/intracytoplasmic sperm injection with GnRH antagonist protocol and triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation.. GnRHa alone versus dual trigger.. Live birth, implantation, and clinical pregnancy rates and OHSS.. The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group.. Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) <4,000 pg/mL improves the probability of conception and live birth without increasing the risk of significant OHSS.

Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Databases, Factual; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embryo Implantation; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Retrospective Studies; Risk Factors

Triggering of final oocyte maturation with gonadotrophin-releasing hormone agonist (GnRHa) has previously been shown to prevent ovarian hyperstimulation syndrome (OHSS), but at the same time a detrimental effect on clinical outcome parameters was usually reported. In this prospective, observational, proof-of-concept study, a new protocol was employed, using GnRHa to trigger final oocyte maturation in OHSS high-risk IVF/ICSI patients after co-treatment with GnRH antagonist. The aim was to avoid cycle cancellation in high-risk patients without increasing the risk of early onset OHSS and simultaneously secure the reproductive outcome. Twelve patients with >or =25 follicles > or =11 mm in diameter after ovarian stimulation were prospectively enrolled to have final oocyte maturation triggered with 0.5 mg buserelin s.c., followed by a single bolus of 1500 IU human chorionic gonadotrophin (HCG) 35 h later to rescue the luteal phase. A mean of 21.5 oocytes was retrieved. All patients underwent embryo transfer, resulting in an ongoing clinical pregnancy rate per cycle of 50% (6/12) and a live birth rate of 50% (6/12). One patient developed moderate, late onset OHSS that did not require hospitalization. GnRHa triggering of final oocyte maturation followed by one bolus of 1500 IU HCG seems to prevent early onset OHSS in high-risk patients and secure the reproductive outcome.

Topics: Adult; Buserelin; Chorionic Gonadotropin; Drug Combinations; Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pilot Projects; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted