Use of Triggers on in vitro Fertilization and Evaluation of Risk Factors for Sub-Optimal Maturation Rate / Uso de gatilhos na fertilização in vitro e avaliação dos fatores de risco para taxa de maturação subótima

Abstract Objective To compare the oocyte maturation rate in the treatment of in vitro fertilization (IVF) in terms of the use of human chorionic gonadotropin (hCG), agonist gonadotropin-releasing hormone (GnRH) and dual trigger and to evaluate the associated risk factors for sub-optimal maturation rates. Methods A retrospective cohort study with 856 women who underwent IVF. They performed oocyte retrieval and were classified into 3 groups (1 - hCG, 2 - GnRHagonist, 3 - dual trigger). The primary outcome was maturation rate per trigger, and the secondary outcomes were the pregnancy rate per oocyte retrieval and the correlations between low maturation rate as well as the clinical and treatment characteristics of women. Results The maturation rate was 77% in group 1; 76% in group 2, and 83% in group 3 (p=0.003). Group 2 showed women with better ovarian reserve, greater number of oocytes collected, and more mature oocytes and embryos compared with the other groups (p<0.001). The cumulative clinical pregnancy rate was no different between the groups (p=0.755). Low ovarian reserve and low doses of follicle-stimulating hormone (FSH) administered during the stimulus were associated with a higher chance of null maturation rate. Conclusion The oocyte maturation rates and IVF results were similar in all groups. Low ovarian reserve is associated with the worst treatment results.

Resumo Objetivo Comparar a taxa de maturação oocitária no tratamento de fertilização in vitro (FIV) emrelação so o uso de gonadotrofina coriônica humana (hCG), agonista de hormônio liberador de gonadotrofina (GnRH), e gatilho duplo e avaliar os fatores de risco associados a taxas de maturação subótimas. Métodos Estudo de coorte retrospectivo com 856 mulheres submetidas à FIV. Elas foram classificadas em 3 grupos (1 - hCG, 2 - GnRH agonista, 3 - gatilho duplo). O desfecho primário foi a taxa de maturação por gatilho, e os desfechos secundários foram a taxa de gravidez por recuperação de oócitos e as correlações entre a baixa taxa de maturação bem como as características clínicas e do tratamento das mulheres. Resultados A taxa de maturação foi de 77% no grupo 1; 76% no grupo 2, e 83% no grupo 3 (p=0,003). O grupo 2 apresentou mulheres com melhor reserva ovariana, maior número de oócitos coletados, oócitosmaduros, e embriões, emcomparação aos demais grupos (p<0,001). A taxa cumulativa de gravidez clínica não foi diferente entre os grupos (p=0,755). Baixa reserva ovariana e baixas doses de hormônio folículoestimulante (FSH) administradas durante o estímulo foram associadas a uma maior chance de taxa de maturação nula. Conclusão As taxas de maturação oocitárias e os resultados de FIV foram semelhantes em todos os grupos. A baixa reserva ovariana está associada aos piores resultados do tratamento.

Tratamiento hormonal de la pedofilia: ¿puede curar la pedofilia con la castración química? / Pedophilia hormonal therapy: can pedophilia be cured with chemical castration

Históricamente la sociedad ha rechazado el abuso sexual de menores de 13 años, dictándose leyes al respecto. La justicia luego de un debido proceso condenaba al victimario con reclusión incluso hasta la década del 70-80, con orquiectomía. Los adelantos en neurobiología, endocrinología, sicofarmacología y sicología se consideraron las bases para tratar al pedófilo y someterlo a libertad condicional, ahorrándose el costo financiero de la reclusión de por vida. Diversos países dictaron leyes contra la conducta pedófila. En dicha legislación ejerció gran influencia la promulgación en EE.UU. (estado de Washington "sobre el ofensor sexual" y el dictamen de la Corte Suprema en 1997 en el juicio de Kansas vs Hendricks). En Chile en los 90 el caso del pedófilo apodado "Zacarach" sacó a la luz pública el tema que no se quería ver. En esa fecha se presentó al parlamento un proyecto de Ley para "curar" la pedofilia con acetato de Medroxiprogesterona imitando legislación de EE.UU. Causó sorpresa en el medio endocrinológico que se usara terapia hormonal como "cura" de la pedofilia. Se ha utilizado en varios países la castración química producida por gestágenos o agonístas del GnRH más antiandrógenos (acetato de Ciproterona), para inhibir la secreción y acción de la testosterona disminuyendo líbido y erección. No se ha demostrado que exista curación de la orientación pedófila y existen dudas de la prevención primaria y secundaria de la pedofilia. Pese al adelanto tecnológico en neurociencias para estudio de las zonas vinculadas a la sexualidad, aún no existen marcadores que permitan diagnosticar o pronosticar futuros resultados de la terapia. El tratamiento médico de la pedofilia no garantiza curación ni prevención del delito pedofílico.

Historically, society has rejected sexual abuse of children under 13, with there having been laws enacted in this regard. The judicial system, after a due process, condemned the perpetrator with reclusion and even up until the decades of the 70s and 80s with orchiectomy. Advances in neurobiology, endocrinology, psychopharmacology and psychology were considered the basis for treating the pedophile and putting them on probation, saving the financial cost of imprisonment for life. Multiple countries have enacted laws against pedophilic behaviour. Such legislation was greatly influenced by the enactment in the USA (state of Washington "on the sex offender" and the ruling of the Supreme Court in 1997 in the trial of Kansas against Hendricks). In Chile in the 90s, the case of a pedophile nicknamed "Zacarach" brought to light an issue that nobody wanted to see. Around that time, a bill was presented to Parliament to try and "cure" pedophilia with Medroxyprogesterone acetate, imitating US legislation. It was a surprise in the endocrinological world that hormonal therapy would be used as a "cure" for pedophilia. Chemical castration produced by gestagens or GnRH agonists plus antiandrogens (Cyproterone acetate) has been used in several countries to inhibit the secretion and action of testosterone, reducing libido and erection. It has not been proven that there is a cure for pedophile orientation and there are doubts about the primary and secondary prevention of pedophilia. Despite technological advances in neurosciences for the study of the zones pertaining to sexuality, there are still no indicators that allow for diagnosis or prediction of future results of therapy. The medical treatment of pedophilia does not guarantee cure or prevention of pedophilic crime.

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.

Técnica de doble disparo (doubble trigger) en pacientes normorrespondedoras con bajo porcentaje de ovocitos maduros / Doubble Trigger in patients with a normal response with a low percentage of mature oocytes

Resumen OBJETIVO: Evaluar el efecto del doble disparo en pacientes con un ciclo previo con menos de 65% de ovocitos maduros respecto de los ovocitos capturados, en una población con respuesta normal a la inducción de la ovulación con hCG recombinante o urinaria. MATERIALES Y MÉTODOS: Estudio de cohorte, prospectivo, efectuado en pacientes con diagnóstico de infertilidad, en tratamiento con fertilización in vitro, evaluadas en el Centro Mexicano de Fertilidad (Hospital Ángeles Lomas) entre 2017 y 2019. El tratamiento se llevó a cabo en la misma paciente, en cuyo ciclo previo convencional con esquema de antagonista e inducción de la ovulación con hCG tuvo respuesta ovárica subóptima y captura ovocitaria con menos de 65% en fase M2 (Grupo 1). Posteriormente se les indicó un segundo ciclo con el mismo esquema de gonadotropinas e inducción de la ovulación con doble disparo: acetato de triptorelina 1 mg + 5000 UI de hCG urinaria 40 y 34 horas previas a la captura (Grupo 2). Se evaluaron el porcentaje y la cantidad de ovocitos capturados en fase M2. RESULTADOS: Se registraron 34 pacientes en quienes se llevaron a cabo 68 ciclos. La cantidad de ovocitos capturados fue mayor en el grupo 2 (agonista de GnRH + hCG urinaria; p = 0.03). El doble disparo aumentó el porcentaje de ovocitos maduros (65.4 ± 21.3 vs 74.6 ± 20.2; p = 0.07). CONCLUSIONES: La técnica de doble disparo es valiosa para el tratamiento de pacientes con captura de ovocitos deficiente, aun con desarrollo folicular normal y concentraciones de estradiol adecuadas y óptimas de hCG el día de la captura. Se requieren estudios prospectivos de gran tamaño para dilucidar la recomendación mencionada de la técnica de "doble disparo".

Abstract OBJECTIVE: To evaluate the effect of double trigger in patients with a previous cycle with less than 65% of mature oocytes compared to the captured oocytes, in a normorresponding population with induction of ovulation with recombinant or urinary hCG. MATERIALS AND METHODS: A prospective cohort study, conducted in patients diagnosed with infertility, treated with in vitro fertilization, evaluated at the Mexican Fertility Center (Hospital Angeles Lomas) between 2017 and 2019. The treatment was carried out in the same patient, in whose previous conventional cycle with antagonist scheme and induction of ovulation with hCG had suboptimal ovarian response and oocyte capture with less than 65% in M2 phase (Group 1). Subsequently, a second cycle was performed with the same scheme of gonadotropins and induction of ovulation with double shot: 1 mg triptorelin acetate + 5000 IU of urinary hCG 40 and 34 hours prior to capture (Group 2 or double trigger). Percentage and quantity of oocytes captured in M2 phase were evaluated. RESULTS: 34 patients were registered, in whom 68 cycles were performed. The number of oocytes captured was greater in group 2 (agonist of GnRH + urinary hCG; p = 0.03). The double shot increased the percentage of mature oocytes 65.4 ± 21.3 vs 74.6 ± 20.2 (p = 0.07). CONCLUSIONS: The double trigger technique is valuable for the treatment of patients with poor oocyte capture, even with normal follicular development and adequate and optimal hCG estradiol concentrations on the day of capture. Large prospective studies are required to elucidate the aforementioned recommendation of the "double shot" technique.

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.

Novel use of GnRH agonist as neoadjuvant treatment for giant endometrial polyps

@#Endometrial polyp, being one of the most common causes of abnormal uterine bleeding, is formed from localized overgrowths of endometrial tissue brought about by increased estrogen levels. Sizes of polyps usually are less than 2cm, while those >4 cm are labeled as giant polyps. Such polyps can even occupy the entire endometrial cavity, making complete hysteroscopic removal difficult and prone to failure and morbidity. Limited literature regarding use of GnRH agonist in endometrial polyps are published, but given the idea that it induces a state of hypoestrogenism, it could be a promising approach for neoadjuvant treatment in such cases. In this paper, 3 cases of giant endometrial polyps with fertility problems were given GnRH agonists prior to resection. All cases have shown significant decrease in size of their polyps, making complete and successful hysteroscopic removal feasible.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty

PURPOSE: Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. METHODS: Patient group included 83 girls (aged 7.0–8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. RESULTS: No statistical difference in BMI z-score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P<0.001). In normal-weight subjects in the patient group, BMI z-score was significantly increased during GnRHa treatment (−0.1±0.7 vs. 0.1±0.8, P<0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z-score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P=0.044). CONCLUSION: Girls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z-scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z-scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

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.

Gonadotropin-Releasing Hormone (GnRH) Agonist Trigger in a GnRH Antagonist Protocol and Severe Ovarian Hyperstimulation Syndrome.

Aims: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life-threatening complication of ovarian stimulation. The best strategy to prevent it is to use a gonadotropinreleasing hormone (GnRH) agonist (GnRHa) to trigger final oocyte maturation in a GnRH antagonist protocol, followed by cryopreservation of all oocytes/embryos (freeze-all strategy). The objective of this study is to describe two cases of a rare occurrence of severe OHSS following GnRHa trigger in a GnRH antagonist protocol and freeze-all strategy. Presentation of Case: Two patients (a 33-year-old patient, and a 31-year old patient) were submitted to in vitro fertilization (IVF). The ovarian stimulation started on day 2 of her menstrual cycle in a step-down GnRH antagonist protocol. The final oocyte maturation was induced with a bolus of 0.2 mg triptorelin in both cases. Due tothe risk of OHSS, all the embryos were cryopreserved and no embryo transfer was performed. In the case 1, two days after oocyte retrieval, the patient was seen at the emergency and was diagnosed with severe OHSS with bilateral pleural effusion. In the case 2, three days after oocyte retrieval, the patient was seen at the emergency unit and was diagnosed with severe OHSS. Both patients were managed in an intensive care unit. Conclusions: Unless the substitution of human chorionic gonadotropin (hCG) by GnRHa triggering in antagonist cycles is done in combination with no embryo transfer (which is the best form of OHSS prevention), and unless it virtually completely eliminates the onset of OHSS, this complication may still occur in certain groups of patients.

Efficacy of Laparoscopic Surgery Combined with GnRH-a in the Treatment of Endometriosis / 中国微创外科杂志

Objective To evaluate the clinical efficacy of laparoscopic surgery combined with GnRH agonist in the treatment of endometriosis. Methods From January 2008 to January 2012, 205 patients with endometriosis underwent conservative laparoscopy surgery in our hospital .According to whether the patients accepted the therapy of GnRH-a and the time of the treatment after surgery, patients were divided into three groups:group A was treated with conservative laparoscopic surgical (73 cases), group B was given GnRH-a for 3 months after surgery (68 cases), and group C received GnRH-a for 6 months after surgery (64 cases).These patients were followed up for 24 months after surgery .The recurrence rate and pregnancy rate were compared among the three groups . Results The postoperative recurrence rates within one year were 4.4%(3/68) in the group B and 3.1% (2/64) in the group C, which were all lower than that of the group A (13.7%, 10/73).There was no difference between the group A and B (χ2 =3.628, P=0.057), while the rate of group C was significantly lower than that of the group A (χ2 =4.771, P=0.029).The cumulative recurrence rates in the group B and C were respectively 13.2%(9/68) and 10.9%(7/64), which were significantly lower than that of the group A [27.4%(20/73); χ2 =4.322, P=0.038; χ2 =5.839, P=0.016].There were no differences about the natural pregnancy rate within 2 years postoperatively among the three groups (χ2 =0.812, P=0.666), but for those who underwent IVF-ET after laparoscopy, the pregnancy rates in group B and C were respectively 78.9% (15/19) and 80.0% (16/20), which were significantly higher than that of the group A [47.6% (10/21); χ2 =4.177, P=0.041; χ2 =4.630, P=0.031]. Conclusions Laparoscopic surgery combined with GnRH-a is highly effective in the treatment of endometriosis , which can effectively reduce the recurrence rate .Application of GnRH-a for 3-6 months after laparoscopic surgery can improve the pregnancy rate in those who accept the treatment of IVF-ET.

Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction / 대한생식의학회지

OBJECTIVE: To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. METHODS: Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. RESULTS: There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. CONCLUSION: Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS.

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.

GnRH Agonist Co-treatment for Prevention of Primary Ovarian Insufficiency in Patients with Hematologic Malignancies Undergoing Chemotherapy / 대한폐경학회지

OBJECTIVES: The aim of this study was to assess the effect of gonadotropin-releasing hormone (GnRH) agonist co-treatment for gonadal protection in patients with hematologic neoplasms undergoing chemotherapy. METHODS: Young premenopausal women who were diagnosed with leukemia or lymphoma between March 2010 and February 2012 and undergoing chemotherapy in a university hospital were included in this study. RESULTS: Twenty-nine patients aged 15.39 years participated in this study. Among the patients, five patients were receiving leuprolide concomitant with chemotherapy, and twenty-four patients were receiving chemotherapy alone. Seventeen patients in the chemotherapy alone group stopped menstrating and were diagnosed with primary ovarian insufficiency (POI) within one year after chemotherapy; and only one patient had POI in the chemotherapy plus leuprolide group, but these differences were not statistically significant (P = 0.054). In the chemotherapy plus leuprolide group, serum anti-mullerian hormone (AMH) levels were significantly lower than basal serum AMH levels (5.57 +/- 0.18 ng/mL) (P < 0.001) after treatment (1.84 +/- 0.22 ng/mL). CONCLUSION: GnRH agonist may be a promising option for the prevention of POF, but the effectiveness of GnRH agonist is still debatable. A large prospective multi-center trial with adequate follow-up is needed.

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.

Ovarian Hyper-Response to Administration of an GnRH-Agonist Without Gonadotropins

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.

GnRH Agonist Therapy to Protect Ovarian Function in Young Korean Breast Cancer Patients

The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.

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.

A case of telangiectasis of the uterus: uncontrolled massive uterine bleeding after gnrh agonist therapy / 대한산부인과학회지

Telangiectasis of the uterus is an extremely rare but life-threatening disease because of massive uterine bleeding. The usage of GnRH agonist can cause regression and atrophy of the endometrium through induction of hypoestrogenism by pituitary down-regulation. But there is no clear explanation or report in the literature showing the relationship between uterine telangiectasis and GnRH agonist usage. We have experienced a patient with uncontrolled massive uterine bleeding after GnRH agonist treatment, who needed emergency hysterectomy. Pathologic tissue examination showed telangiectasis of the endometrium and myometrium. This is the first case report of telagiectasis of the uterus without other organ involvement. We report this case with a brief review of the literatures.