Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study

Background & objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration. Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05). Interpretation & conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Corifollitropin Alfa for Controlled Ovarian Stimulation in Assisted Reproductive Technologies: State of the Art / Alfacorifolitropina para estimulação ovariana controlada em tecnologias de reprodução assistida: Estado da arte

Abstract Physical and emotional burdens during the journey of infertile people through assisted reproductive technologies are sufficient to justify the efforts in developing patient-friendly treatment strategies. Thus, shorter duration of ovarian stimulation protocols and the need for less injections may improve adherence, prevent mistakes, and reduce financial costs. Therefore, the sustained follicle-stimulating action of corifollitropin alfa may be the most differentiating pharmacokinetic characteristic among available gonadotropins. In this paper, we gather the evidence on its use, aiming to provide the information needed for considering it as a first choice when a patient-friendly strategy is desired.

Resumo O desgaste físico e emocional durante a jornada de pessoas inférteis pelas tecnologias de reprodução assistida é suficiente para justificar esforços no desenvolvimento de estratégias de tratamento compassivas. Desta forma, a menor duração dos protocolos de estimulação ovariana e a necessidade de menos injeções podem melhorar a adesão, prevenir erros e reduzir custos financeiros. Portanto, a estimulação folicular sustentada da alfacorifolitropina parece ser a característica farmacocinética que melhor a diferencia das gonadotrofinas atualmente disponíveis no mercado. No presente artigo, reunimos evidências sobre seu uso, com o objetivo de fornecer as informações necessárias para considerá-la como primeira escolha quando se deseja uma estratégia amigável ao paciente.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients / Prevenção da ovulação prematura por meio da administração de antagonismo de liberação de gonadotropismo no dia seguinte à ovulação

Abstract Objective The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. Methods This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. Results The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p=0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p=0.013), the oocyte maturity rate (79.42 versus 47.87%) (p=0.041), the fertilization rate (65.68 versus 34.54%) (p=0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p=0.003) were higher in the GnRH antagonist group than in the control group. Conclusion The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

Resumo Objetivo O objetivo do presente estudo retrospectivo foi investigar a eficácia da administração do antagonista do hormônio liberador da gonadotrofina (GnRH) em dose única no dia seguinte ao desencadeamento da gonadotrofina coriônica humana (hCG) para a maturação final do oócito, na prevenção da luteinização prematura em pacientes com diminuição do ovário reserva em ciclos de fertilização in vitro (FIV). O objetivo secundário do estudo foi pesquisar o efeito deste protocolo nos resultados da gravidez. Métodos Trata-se de um estudo retrospectivo incluindo 267 pacientes inférteis que apresentam um único folículo antral visto por ultrassonografia no 2° ou 3° dia do ciclo menstrual antes de iniciar o tratamento de FIV. Nós randomizamos os pacientes em dois grupos. Os pacientes que receberam injeção de antagonista de GnRH em dose única no dia seguinte ao desencadeamento do hCG formaram o grupo caso, e os pacientes que receberam o regime de tratamento padrão formaram o grupo controle. Em ambos os grupos, os oócitos foram coletados 36 horas após a injeção de hCG. Resultados A taxa de ovulação prematura foi significativamente baixa no grupo caso em comparação com o grupo controle (6,86 versus 20,6% por ciclo programado) (p=0,022). Além disso, a taxa de recuperação de oócitos (93,14 versus 67,87% por ciclo programado) (p=0,013), a taxa de maturidade do oócito (79,42 versus 47,87%) (p=0,041), a taxa de fertilização (65,68 versus 34,54%) (p=0,018) e a taxa de transferência de embriões por ciclo programado (44,11 versus 18,78%) (p=0,003) foram maiores no grupo antagonista de GnRH do que no grupo controle. Conclusão A administração de antagonista de GnRH, no dia seguinte ao desencadeamento de hCG em tratamentos de FIV de pacientes com reserva ovariana diminuída permitiu uma redução significativa na taxa de ovulação precoce,mas não teve efeito na taxa de nascidos vivos.

Is there a perfect protocol for patients with low ovarian reserve: a retrospective study comparing antagonist or agonist protocol in patients with low ovarian reserve

Background: The high prevalence of infertility has made it a major healthcare problem in the present era. A majority of patients presenting with infertility have poor ovarian reserve (POR). Patients with POR are challenging to treat due to reduced treatment success and high cycle cancellation rate as there is no uniform definition and treatment protocol for these patients. The present retrospective study was performed to compare the pregnancy outcome between a long agonist protocol and flexible antagonist protocol in patients with POR. Patients with AMH ≤1.5 ng/mL and AFC ≤4 was included in the study. Controlled ovarian hyperstimulation is the basis of any in vitro fertilisation (IVF) procedure. There is no universally accepted ideal stimulation protocol for patients with POR, and it remains a challenge.Methods: This was a retrospective study covering the period from May 2019 to March 2020. Ninety-nine patients with low ovarian reserve (AMH ≤1.5 ng/mL and AFC ≤4) were included in the study. The patients underwent GnRH agonist/GnRH antagonist stimulation protocol using recombinant FSH. Demographic characteristics like age, BMI, duration of infertility was comparable. Total days of stimulation, total Gonadotropin dose used and clinical pregnancy rate in both the protocols was analyzed. Difference between the two groups was considered statistically significant at p-value <0.05.Results: Fifty-three patients underwent antagonist stimulation protocol and forty-six long agonist protocol. The clinical pregnancy rate was 37.7% (20/53) and 32.6% (15/46) in antagonist and agonist protocol respectively (p-value=0.5983). Pregnancy rate was higher in the antagonist group but the difference was not statistically significant.Conclusions: Antagonist protocol could marginally increase pregnancy rate in patients with low ovarian reserve. However, patients with poor ovarian reserve require a tailor-made protocol.

Role of the proportion of dominant follicles in patients with polycystic ovary syndrome undergoing in vitro fertilization-embryo transfer / 中华医学杂志(英文版)

Background@#There is no absolute consensus for the best time for triggering. The aim of this study was to investigate the effect of different proportion of dominant follicles (PDF) on the human chorionic gonadotropin (HCG) day for the clinical outcomes in patients with polycystic ovary syndrome (PCOS) of different ovarian stimulation protocols.@*Methods@#A total of 371 cycles of the gonadotropin-releasing hormone (GnRH) agonist long protocol and 347 cycles of GnRH antagonist protocol from January 2014 to December 2016 were included in this retrospective study. Based on the PDF on the day of the HCG administration, the included patients were divided into three groups: Group A (low PDF), PDF <20%; Group B (medium PDF), 20%≤ PDF ≤40%; Group C (high PDF), PDF >40%. The measurements regarding ovarian stimulation characteristics, fertilization rate, top quality embryo rate, clinical pregnancy rate, and ovarian hyperstimualtion syndrome (OHSS) rate were compared in different PDF groups with different protocols.@*Results@#In both the GnRH antagonist protocol and GnRH agonist long protocol, the characteristics such as mean age, anti-Mullerian hormone, antral follicle count (AFC), and body mass index were comparable between groups. The number of oocytes retrieved decreased statistically significantly as the PDF and rate of matured oocytes increased. In the GnRH agonist long protocol, the rate of normally fertilized oocytes was highest in Group A (59.74 ± 31.21 vs. 49.70 ± 37.95, 49.67 ± 36.62; F = 3.743, P = 0.025). There were no significant differences in the rate of top-quality embryos and the clinical pregnancy rate between the groups. The clinical pregnancy rate was similar in the three groups (63.6%, 62.5%, 67.5%, respectively, χ2 = 0.989, P = 0.911). The moderate and severe OHSS rate increased statistically significantly when the PDF increased, which was highest in group C (1.4%, 3.1%, 6.7%, respectively, χ2 = 12.014, P = 0.017). In the GnRH antagonist protocol, there were no significant differences in the rate of top-quality embryos, the rate of normally fertilized oocytes, the clinical pregnancy rate, and the moderate and severe OHSS rate between the groups. The clinical pregnancy rate in Group C was higher than that in Group A (57.9% vs. 46.6%, χ2 = 10.850, P = 0.093).@*Conclusions@#In the GnRH antagonist protocol, PDF on the HCG day of less than 20% may be unfavorable to the clinical pregnancy rate in PCOS. In the GnRH agonist long protocol, delaying the HCG trigger timing has no good effect on clinical pregnancy and the risk of OHSS might increase in patients with PCOS.

Effects of different controlled ovarian stimulation protocols on preimplantation genetic testing outcomes of chromosomal translocation carriers / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the effects of GnRH agonist and antagonist protocols on preimplantation genetic testing outcomes of chromosomal translocation carriers.METHODS: The clinical data of 226 patients with chromosomal translocation were analyzed retrospectively between Jan. 2015 and Dec. 2017 in Shengjing Hospital Affiliated to China Medical University.The patients were divided into GnRH agonist group(174 cases)and GnRH antagonist group(52 cases),then the duration of gonadotropin stimulation,dosage of gonadotropin used,embryonic quality,normal and balanced embryo numbers,per transfer cyclepregnancy rate,abortion rate and continuous pregnancy rate and accumulated pregnancy rate were analyzed.RESULTS: There were no statistical differences in the number of retrieved oocytes,number of MⅡ oocytes,fertilization rate,cleavage rate,blastocyst formation rate,number of high-quality embryo,number of blastocyst biopsy,normal and balanced embryo numbers,per transfer cycle pregnancy rate,abortion rate,continuous pregnancy rate or accumulated pregnancy rate between GnRH agonist group and GnRH antagonist group(P>0.05).The duration of gonadotropin stimulation(9 d vs. 10 d)and dosage of gonadotropin(2100 U vs. 2400 U)used in the GnRH antagonist group were significantly less than the GnRH agonist group(P<0.05).CONCLUSION: There are no significant differences in embryo quality or pregnancy rate between the GnRH agonist group and antagonist group during preimplantation genetic testing,but the GnRH antagonist group have an advantage in Gn duration and dosage.

Tasa acumulada de embarazo clínico y en curso en ciclos de inseminación intrauterina y análisis de los ciclos según la edad, conteo de folículos maduros y estimulación con antagonista de GnRH / Clinical and ongoing cumulative pregnancy rates in cycles of intrauterine insemination and analysis of the cycles according to age, follicular count and GnRH antagonist use

Resumen Objetivo: Determinar la tasa acumulada de embarazo clínico en ciclos de inseminación intrauterina en pacientes estimuladas con gonadotropinas según el número de folículos maduros desarrollados y edad, así como la influencia de los antagonistas de GnRH en su desarrollo y en la tasa de embarazo. Materiales y métodos: Estudio analítico, retrospectivo, en el que se evaluaron ciclos de inseminación intrauterina de pacientes con diferentes protocolos de gonadotropinas en un periodo de dos años. La muestra se dividió en grupos: menores de 35 y más o menos mayores de 35 años y uso o no de antagonista de GnRH. Resultados: Se evaluaron 229 ciclos de inseminación intrauterina en 172 pacientes; de éstas 64% eran menores de 34 años (grupo 1) y 36% mayores de 35 años. El 50% de las pacientes desarrolló de 2 a 3 folículos maduros y 10% de 4 a 6, con una tendencia en aumento de la tasa de embarazo con el desarrollo de hasta 4 folí culos maduros. El antagonista de GnRH no parece relacionarse con mejores tasas de embarazo clínico o en curso en ciclos con más de un folículo maduro. La tasa acumulada de embarazo clínico en tres ciclos fue de 40.6%, mientras que la tasa acumulada de embarazo en curso fue 26.1%. Conclusiones: Hubo relación proporcional entre el número de folículos maduros desarrollados y la tasa de embarazo clínico y en curso. La edad no parece haber tenido influencia en las tasas de em barazo y no pudo demostrarse la eficacia del antagonista en ciclos con desarrollo multifolicular.

Abstract Objective: To determine the cumulative clinical pregnancy rate in cycles of intrauterine insemination with gonadotropin stimulation in relation to number of mature follicles and age and the use of GnRH antagonist on its development. Materials and methods: Analytical, retrospective study in which intrauterine insemination cycles of patients with different gonadotropin protocols were evaluated over a period of two years. The patients were divided in two groups: <35 and ≥35 years old and the use of GnRH antagonist. Results: We evaluated 229 cycles of intrauterine insemination in 172 patients; Of these 64% were under 34 years old (group 1) and 36% over 35 years. The use of antGnRH did not appear to have relation with better clinical and ongoing pregnancy rates in cycles with more than one mature follicle. The cumulative pregnancy rate in three cycles was 40.6%, and cumulative ongoing pregnancy rates was 26.1%. Conclusions: The more mature follicle developed the higher clinical and ongoing pregnancy rates. The age did not appear to have influence in the pregnancy rates, there is no better pregnancy rates with use of antGnRH in cycles with multifolicular developed.

Outcomes of GnRH Agonist and GnRH Antagonist Regimens for IVF in Women Aged up to 40.

Objective: To compare outcomes among good-prognosis patients undergoing in vitro fertilization and intracytoplasmic sperm injection followed by embryo transfer (IVF/ ICSI-ET) in GnRH-agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) regimens. Methods: Retrospective analysis of 434 IVF/ICSI-ET cycles performed in a private center, in women aged up to 40: GnRH-a (n = 291) and GnRH-ant (n = 143). Pregestational, gestational and perinatal outcomes were evaluated. Statistical analysis was performed by unpaired t-test, Mann-Whitney test and Fisher’s exact test. Significance was set at p < 0.05. Results: GnRH-a regimen was associated with higher amounts of total oocytes (10.7 ± 5.7 vs 9.3 ± 5.7, p < 0.001), mature oocytes (8.2 ± 4,5 vs 6.8 ± 4.4, p < 0.001) and good quality embryos transferred (1.7 ± 0.8 vs 1.5 ± 0.9; p < 0.05). Rates of fertilization, embryo implantation and live births were also higher in GnRH-a (72.8%, 27.6% and 48.8%, respectively) compared to GnRH-ant (65.3%, 14.7% and 26.6%, respectively; p < 0.0001). There were no significant differences between rates of preterm delivery or low birth weight, comparing the two groups. Conclusion: Our results suggest that the long GnRH-a regimen is the one that offers the best reproductive outcomes among in women aged up to 40 undergoing IVF/ICSI-ET.

Effectiveness of Gonadotropin-Releasing Hormone Antagonists in the Management of Multifollicular Recruitment in Intrauterine Insemination Cycles.

Introduction: To evaluate the efficacy of GnRH antagonists in terms of increasing the pregnancy rates in intrauterine insemination (IUI) after controlled ovarian stimulation (COS) when more than one dominant follicle is recruited. Methods: This is a prospective and randomized clinical trial that included 300 couples with primary or secondary infertility that underwent their first or second COS-IUI cycle with recombinant FSH. In all of these patients two or three leading follicles > 14 mm of mean diameter where detected by vaginal ultrasound (US) and were randomized into two groups. In group A the patients received rFSH+GnRH antagonists until the day that the hCG was given, while in group B the patients followed a standard COS received rFSH only. Results: Total amount of rFSH units (620.8+245.1vs 575.5+296.4) and clinical pregnancy rates (31.16% vs 19.15%) were statistically significantly higher in patients who were treated with GnRH antagonists. A similar number of twin pregnancies and miscarriages occurred in both groups. Conclusion: Multiple doses of GnRH antagonists in COS-IUI significantly increase pregnancy rates in multifollicular cycles.

The applications of double stimulations and mild ovarian stimulation with GnRH-antagonist in patients with decreased ovarian reserve / 安徽医科大学学报

Objective To discuss the value of double stimulations and mild ovarian stimulation combined with Gn-RH-antagonist in patients with decreased ovarian reserve receiving in vitro fertilization and embryo transfer ( IVF-ET) . Methods 283 patients with decreased ovarian reserve who accepted in vitro fertilization were analyzed retro-spectively. 204 cases accepted double stimulations and 79 cases accepted mild ovarian stimulation combined with GnRH-antagonist, compared the outcomes of the two protocols. Results The average number of oocytes retrieved, viable embryos,high-quality embryos,consumption and duration of Gn,the serum progesterone( P) level on trigger day in the luteal phase were significantly higher than those in follicular phase. The serum luteinizing hormone( LH) level on trigger day was lower than that in follicular phase. The average number of oocytes retrieved,high-quality embryos,consumption and duration of gonadotropins( Gn) in mild stimulation combined with GnRH-antagonist were higher than those in follicular phase. LH level on trigger day was lower than those in follicular phase, while the numbers of viable embryos were similar. The consumption and duration of Gn in the luteal phase were higher than in stimulation combined with GnRH-antagonist, and there were no differences in the average number of oocytes re-trieved,viable embryos,high-quality embryos between the two groups. The cycle cancellation rate, available rate of oocytes and embryos were similar between the controlled ovarian hyperstimulation. The available rate of embryos in double stimulations was higher than mild ovarian stimulation combined with GnRH-antagonist,and the abortion rate was lower. Conclusion Controlled ovarian hyperstimulation during luteal phase can get better outcomes in patients with decreased ovarian reserve,double stimulations in the same menstrual cycle shortens the treatment time of IVF-ET,and it is a feasible method for patients with decreased ovarian reserve.

Effect of GnRH antagonists on clinical pregnancy rates in ovulation induction protocols with gonadotropins and intrauterine insemination

<p><b>INTRODUCTION</b>Intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) was applied to selected infertile patients to determine the effect of gonadotropin-releasing hormone (GnRH) antagonists in IUI cycles, in which recombinant follicle-stimulating hormone (rFSH) had been used for COH.</p><p><b>METHODS</b>This study was conducted between April 1, 2009 and June 10, 2009, and involved a total of 108 patients. These patients had primary or secondary infertility, which resulted in an indication for IUI, and they each received two cycles of ovarian stimulation treatment with clomiphene citrate. The patients were randomised into two groups--patients in group A received rFSH + GnRH antagonist (n = 45), while those in group B received only rFSH (n = 63).</p><p><b>RESULTS</b>The mean age of the patients was 31.84 ± 3.73 years and the mean body mass index (BMI) was 24.40 ± 1.88 kg/m(2). The mean age and BMI of the patients in groups A and B were not significantly different. There was no significant difference in the mean total rFSH dose administered (988.33 IU in group A and 871.83 IU in group B). When compared to group B, the mean number of follicles that were > 16 mm on the human chorionic gonadotropin (HCG) trigger day was significantly higher in group A (1.58 and 1.86, respectively; p < 0.05). When the two groups were compared, there were no statistically significant differences in the number of cancelled cycles due to premature luteinisation (none in group A vs. two in group B) and the rate of clinical pregnancy (8.9% in group A vs. 7.9% in group B).</p><p><b>CONCLUSION</b>No significant improvement in the clinical pregnancy rates was observed when GnRH antagonists were used in COH + IUI cycles, despite the significant increase in the number of follicles that were > 16 mm on HCG trigger day.</p>

IVF-ET Outcome Comparison Between GnRH Antagonist Protocol and GnRH Agonist Long Protocol in Treating PCOS Patients / 医药导报

Objective To compare in vitro fertilization and embryo transfer( IVF-ET ) outcome of gonadotropin-releasing hormone( GnRH ) antagonist protocol and GnRH agonist long protocol in patients with polycystic ovary syndrome ( PCOS)and to provide reference for rational selection of ovulation stimulation protocol for PCOS patients. Methods One hundred and four patients with PCOS who underwent IVF-ET were randomly divided into two groups. In the study group,41 patients were subjected to the GnRH antagonist protocol;In the control group,63 patients were subjected to a long protocol of GnRH agonist. Doses and duration of gonadotropin therapy,the thickness of endometrium and the profile of hormone level on the day of HCG administration,the number of retrieved oocytes,the ratio of fertilization,the ratio of cleavage,the ratio of the good quantity embryos,implantation rate of embryo,pregnancy rate,the cycle cancellation rate and the incidence rate of ovarian hyperstimulation syndrome( OHSS)were recorded. Results The IVF-ET outcome of the two groups was similar with respects to the number of oocytes,the ratio of fertilization,the ratio of cleavage,implantation rate of embryo and the pregnancy rate( P﹥0. 05). Significant differences were found(P﹤0. 05)between the two groups regarding to the doses and duration of gonadotropin therapy,the levels of serum E2 and LH on the day of HCG administration,and the cycle cancellation rate. The incidence rate of OHSS was not significantly different ( 2. 44% vs. 12. 70%) between the two groups. Conclusion The duration of gonadotropins administration,the cycle cancellation rate,incidence of OHSS and the financial burdern are reduced in patients treated with GnRH antagonist. The growth of follicle,the ratio of fertilization,the ratio of cleavage,implantation rate of embryo and the pregnancy rate are not different between the two methods. The GnRH antagonist protocol is optimal for patients with PCOS.

Early gonadotropin-releasing hormone antagonist start improves follicular synchronization and pregnancy outcome as compared to the conventional antagonist protocol / 대한생식의학회지

OBJECTIVE: To assess whether an early GnRH antagonist start leads to better follicular synchronization and an improved clinical pregnancy rate (CPR). METHODS: A retrospective cohort study. A total of 218 infertile women who underwent IVF between January 2011 and February 2013. The initial cohort (Cohort I) that underwent IVF between January 2011 and March 2012 included a total of 68 attempted IVF cycles. Thirty-four cycles were treated with the conventional GnRH antagonist protocol, and 34 cycles with an early GnRH antagonist start protocol. The second cohort (Cohort II) that underwent IVF between June 2012 and February 2013 included a total of 150 embryo-transfer (ET) cycles. Forty-three cycles were treated with the conventional GnRH antagonist protocol, 34 cycles with the modified early GnRH antagonist start protocol using highly purified human menopause gonadotropin and an addition of GnRH agonist to the luteal phase support, and 73 cycles with the GnRH agonist long protocol. RESULTS: The analysis of Cohort I showed that the number of mature oocytes retrieved was significantly higher in the early GnRH antagonist start cycles than in the conventional antagonist cycles (11.9 vs. 8.2, p=0.04). The analysis of Cohort II revealed higher but non-significant CPR/ET in the modified early GnRH antagonist start cycles (41.2%) than in the conventional antagonist cycles (30.2%), which was comparable to that of the GnRH agonist long protocol cycles (39.7%). CONCLUSION: The modified early antagonist start protocol may improve the mature oocyte yield, possibly via enhanced follicular synchronization, while resulting in superior CPR as compared to the conventional antagonist protocol, which needs to be studied further in prospective randomized controlled trials.

Cessation of gonadotropin-releasing hormone antagonist on triggering day in flexible multiple-dose protocol: A randomized controlled study / 대한생식의학회지

OBJECTIVE: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. METHODS: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. RESULTS: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5+/-0.9 vs. 3.2+/-0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. CONCLUSION: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.

Effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase compared with GnRH agonist long protocol in non-obese and obese patients with polycystic ovary syndrome undergoing IVF/ICSI / 대한생식의학회지

OBJECTIVE: To evaluate the effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF. METHODS: Two hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH antagonist MDP-EL (antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups. RESULTS: Total dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antagonist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the antagonist group. Similar findings were also observed in obese PCOS subgroup. CONCLUSION: GnRH antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

Comparison of assisted reproductive technology outcomes in infertile women with polycystic ovary syndrome: In vitro maturation, GnRH agonist, and GnRH antagonist cycles / 대한생식의학회지

OBJECTIVE: We compared the assisted reproductive technology (ART) outcomes among infertile women with polycystic ovary syndrome (PCOS) treated with IVM, conventional IVF, GnRH agonist, and GnRH antagonist cycles. METHODS: The prospective study included a total of 67 cycles in 61 infertile women with PCOS. The women with PCOS were randomized into three IVF protocols: IVM/IVF with FSH and hCG priming with immature oocyte retrieval 38 hours later (group A, 14 cycles), GnRH agonist long protocol (group B, 14 cycles), and GnRH antagonist multi-dose flexible protocol (group C, 39 cycles). IVF outcomes, such as clinical pregnancy rate (CPR), implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR), were compared among the three groups. RESULTS: Age, BMI, and basal FSH and LH levels did not differ among the three groups. The number of retrieved oocytes and 2 pronucleus embryos was significantly lower in group A compared with groups B and C. The CPR, IR, MR, and LBR per embryo transfer showed no differences among the three groups. There was no incidence of ovarian hyperstimulation syndrome in group A. CONCLUSION: The IR, MR, and LBR in the IVM cycles were comparable to those of the GnRH agonist and GnRH antagonist cycles. The IVM protocol, FSH and hCG priming with oocyte retrieval 38 hours later, is an effective ART option that is comparable with conventional IVF for infertile women with PCOS.

Cessation of Gonadotropin-Releasing Hormone Antagonist on Triggering Day: An Alternative Method for Flexible Multiple-Dose Protocol

This study was performed to analyze retrospectively outcomes of stimulated in vitro fertilization (IVF) cycles where the gonadotropin-releasing hormone (GnRH) antagonist was omitted on ovulation triggering day. A total of 92 consecutive IVF cycles were included in 65 women who are undergoing ovarian stimulation with recombinant FSH. A GnRH antagonist, cetrorelix 0.25 mg/day, was started when leading follicle reached 14 mm in diameter until the day of hCG administration (Group A, 66 cycles) or until the day before hCG administration (Group B, 26 cycles). The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and the number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in Group B compared to Group A (2.7+/-0.8 vs. 3.2+/-0.9 ampoules). There was no premature luteinization in the subjects. The proportion of mature oocytes (71.4% vs. 61.7%) and fertilization rate of mature (86.3+/-19.7% vs. 71.8+/-31.7%) was significantly higher in Group B. There were no significant differences in embryo quality and clinical pregnancy rates. Our results suggest that cessation of the GnRH antagonist on the day of hCG administration during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising IVF results.

Preservation of ovarian follicle by concomitant administration of GnRH agonist I, II or GnRH antagonist during Cyclophosphamide or Paclitaxel chemotherapy in mice / 대한산부인과학회지

OBJECTIVE: The degree of destruction of primordial follicles was investigated following the administration of cyclophosphamide or paclitaxel respectively in mouse ovaies. And then the effect of GnRHa I, GnRH antagonist and GnRHa II on the primordial follicles was evaluated following the administration of cyclophosphamide or paclitaxel. METHODS: Saline or cyclophosphamide (50 mg/kg or 75 mg/kg) were intraperitoneally injected into seven-week old female ICR mice. GnRHa I (Leuplin(R)), GnRH antagonist (Cetrotide(R)) or GnRHa II (H-6038) was injected into mice, and administered with 50 mg/kg and 75 mg/kg of cyclophosphamide following 9 days treatment with GnRH analogues. After collecting ovaries, H&E staining was performed and the number of primordial follicles was counted. To confirm the induction of apoptosis, TUNEL assay was performed. Another experimental groups of mice were administered with a low concentration (12.5 mg/kg) or a high concentraion (19 mg/kg) of paclitaxel. RESULTS: Cyclophosphamide and paclitaxel cause mild to moderate destruction of primordial follicles in mouse ovaries. The number of primordial follicles in the group of high dose was noted less than in that of low dose treated with cyclophosphamide or paclitaxel. Increased the apoptotic indices were shown in the group of cyclophosphamide or paclitaxel compared to in saline only treated group. Treatment with GnRHa I, GnRH antagonist and GnRHa II significantly increased the number of primordial follicles at a low concentration of cytotoxic agents (P<0.05), whereas the number of primoridal follicle increased only in GnRHa I antagonist treated group at a high concentration of cyclophosphamide or paclitaxel (P<0.05). CONCLUSION: The present study shows that GnRH analogues alleviate destruction of primordial follicles caused by cyclophosphamide and paclitaxel in mouse ovaries, suggesting that GnRH analogues may be applicable to increase fertility opportunity in malignant cancer patients of reproductive age planning future pregnancies.

Comparison between a GnRH Agonist and a GnRH Antagonist Protocol for the Same Patient Undergoing IVF / 华中科技大学学报（医学）（英德文版）

Summary: In order to compare GnRH agonist with antagonist protocol for the same patient during controlled ovarian stimulation cycles, the in vitro fertilization and embryo transfer (IVF-ET) outcome was retrospectively studied in 81 patients undergoing 105 agonist protocols and 88 antagonist protocols. The results showed that there was no statistically significant difference in duration of ovarian stimulation, number of ampoules, oocytes retrieved, serum estradiol (E2) and progesterone (P) levels,thickness of endometrium, the zygote-and blastocyst-developmcnt rate between GnRH agonist and antagonist protocols (P>0.05). High quality embryo rate was higher in antagonist protocols, but there was no significant difference between two protocols. Implantation rate and clinical pregnant rate were significantly higher in antagonist protocol (15.82% and 30.26%, respectively) than in agonist protocol (5.26% and 10.64% respectively (P<0.05). It was concluded GnRH antagonist protocol probably improved the outcome of pregnancy of older patients with a history of multiple failure of IVF-ET in a GnRH protocol.

Clinical correlation of basal FSH level and IVF-ET outcome / 대한산부인과학회지

OBJECTIVE: The objective of this study is to evaluate the value of basal follicular stimulating hormone level on clinical outcome in women undergoing IVF-ET. METHOD: A descriptive and retrospective study of 730 cycles of IVF-ET chosen from 2002 to 2004 in CHA fertility center. RESULTS: Basal FSH screening appeared to be a fairly informative predictor of achiving pregnancy especially in GnRH agonist long protocol in women undergoing IVF-ET. In addition, basal FSH level shows significant difference compared ongoing pregnancy with early abortion group in GnRH antagonist group. CONCLUSION: Therefore, we were able to predict the ovarian response and IVF-ET outcome using FSH level. Furthermore, this information allow more precise counseling for patients.