Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy

BACKGROUND Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis.AIM To evaluate the outcomes of young hormone receptor(HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy(NAC),and the oncologic efficacy of gonadotropin-releasing hormone(GnRH)agonists.METHODS This retrospective study involved a prospectively enrolled cohort.We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017.Among patients with HR-positive and human epidermal grow factor 2(HER2)-negative breast cancer,we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years.RESULTS Among 431 patients with NAC and HR-positive/HER2-negative breast cancer,78 were 35 years old or younger,and 353 patients were older than 35 years.The median follow-up was 71.0 months.There was no statistically significant difference in disease free survival(DFS,P=0.565)and overall survival(P=0.820)between the patients equal to or younger than 35 years and the patients older than 35 years.The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group(52.4%vs 11.2%,P<0.001).Interestingly,for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years,patients treated with the GnRH agonist had better DFS(P=0.037).CONCLUSION Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Influence of Different Gonadotropin-releasing Hormone Agonist Administration Methods on Pregnancy Outcomes of Patients Undergoing In-vitro Fertilization-embryo Transfer

This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.

Artificial Cycle with or without a Depot Gonadotropin-releasing Hormone Agonist for Frozen-thawed Embryo Transfer： An Assessment of Infertility Type that Is Most Suitable

The clinical outcomes of five groups of infertility patients receiving frozen- thawed, cleavage-stage embryo transfers with exogenous hormone protocols with or without a depot gonadotropin-releasing hormone （GnRH） agonist were assessed. A retrospective cohort analysis was performed on 1003 cycles undergoing frozen-thawed, cleavage-stage embryo transfers from January 1, 2012 to June 31, 2015 in the Reproductive Medicine Center of Wuhan General Hospital of Guangzhou Military Region. Based on the infertility etiologies of the patients, the 1003 cycles were divided into five groups： tubal infertility, polycystic ovary syndrome （PCOS）, endometriosis, male infertility, and unexplained infertility. The main outcome was the live birth rate. Two groups were set up based on the intervention： group A was given a GnRH agonist with exogenous estrogen and progesterone, and group B （control group） was given exogenous estrogen and progesterone only. The results showed that the baseline serum hormone levels and basic characteristics of the patients were not significantly different between groups A and B. The live birth rates in groups A and B were 41.67% and 29.29%, respectively （P〈0.05）. The live birth rates in patients with PCOS in groups A and B were 56.25% and 30.61%, respectively （P〈0.05）. The clinical pregnancy, implantation and on-going pregnancy rates showed the same trends as the live birth rates between groups A and B. The ectopic pregnancy rate was significantly lower in group A than in group B. We concluded that the live birth rate was higher and other clinical outcomes were more satisfactory with GnRH agonist co- treatment than without GnRH agonist co-treatment for frozen-thawed embryo transfer. The GnRH agonist combined with exogenous estrogen and progesterone worked for all types of infertility tested, especially for women with PCOS.

Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients

Background Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients＇ future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists （GnRHa） cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients. Methods Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People＇s Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy （n=5） without GnRHa or were historical controls （n=11）. The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups. Results There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One （1/16） patient in the study group while 2 （2/16） patients in the control group relapsed 2 years after conclusion of the primary treatment （P 〉0.05）. All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment （P 〈0.05）. There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy. Conclusions GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.

Effects of gonadotropin-releasing hormone antagonists on the expression of vascular endothelial growth factor and its receptors in a rat model of ovarian hyperstimulation syndrome

Background Ovarian hyperstimulation syndrome （OHSS） is one of the most life-threatening complications of assisted reproduction treatments. Gonadotropin-releasing hormone antagonists （GnRHanta） are thought to be effective in preventing this complication, and some clinical trials have found lower incidences of OHSS in patients treated with GnRHanta. Our aim was to investigate the effects of GnRHanta on vascular permeability and the expression of vascular endothelial growth factor （VEGF） and its receptors in a rat model of OHSS. Methods An immature early OHSS rat model was established. Three ovarian stimulation protocols were used： pregnant mare serum gonadotropin/human chorionic gonadotropin （hCG） alone, with a GnRHanta, or with a gonadotropin-releasing hormone agonists （GnRHa）. Blood and tissue samples were collected at 48 hours after hCG administration. Vascular permeability was evaluated by measuring the Evans-Blue content of extravasated peritoneal fluids. The expression of VEGF and its receptors, including fit-1 and KDR, were detected by reverse transcriptase-polymerase chain reaction and Western blotting. Results Treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF and its two receptors. However, GnRHanta treatment caused a greater reduction in serum estradiol concentrations, and in VEGF receptor mRNA expression than GnRHa. There were no significant reductions in the expression of VEGF or its receptors in extra-ovarian tissues, including the liver, lungs and peritoneum. Conclusion Our results reveal that GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries.

子宫内膜异位症术后GnRH-a治疗与黑升麻制剂的使用

子宫内膜异位症(EMS)是临床上最常见的妇科疾病之一,术后的复发问题一直困扰着临床医师。促性腺激素释放激素激动剂(GnRH-a)的使用对于降低EMS术后的复发具有十分重要的作用,目前已成为临床上最为常用的预防EMS复发的方法。但是,GnRH-a使用后引发的围绝经期症状严重影响患者的生活质量,部分患者因此而终止治疗。激素反向添加治疗虽然很好的解决了围绝经期症状,但是激素的长期使用可能导致激素依赖性疾病的风险。作为一种植物提取物,黑升麻制剂能否较好的拮抗GnRH-a所致类围绝经期症状,而且又能避免激素反向添加治疗的风险,目前尚不明确。该文主要围绕EMS术后GnRH-a治疗的必要性及其存在的问题,黑升麻制剂的作用机制与功能,黑升麻用于缓解EMS患者术后使用GnRH-a治疗出现的类围绝经期症状的可能性及可能存在的问题进行概述。

A Case of Thromboembolism After Injection of Gonadotropin-releasing Hormone Agonist

Gonadotropin-releasing hormone agonist （GnRH-a） was one of the most used therapies in the treatment of endometriosis. But unfortunately, no literatures realized GnRH-a may be related to thrombosis until now. The case below was exactly about thromboembolism taking place after using GnRH-a because ofestradiol （E2） peak short-time after injection.

Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality.The effect of chemotherapy can range from minimal effects to complete ovarian atrophy.Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility.Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufficiency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function.Notably,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological malignancies.Furthermore,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor status.In addition,studies on hematological malignancies have yielded negative results;nevertheless,thefindings must be interpreted with caution owing to numerous limitations.Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible.In this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisfield that upcoming research should focus on.

Studies of GnRH-A Active Immunization Effects on LH and FSH Secretion and Histostructure of the Ovary and Uterus in Rabbits

The objective of the study is to investigate the effects of active immunization against gonadotropin releasing hormone agonist （GnRH-A） on secretion of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） in the pituitary, and to observe the histological structures and development about ovaries and uteri in female rabbits. 24 female rabbits （Oryctolagus cuniculus） were divided randomly into 4 groups （n=6）, namely, experimental group I （EG-I）, experimental II （EG-II）, experimental III （EG-III）, and control group （CG）. Rabbits were subcutaneously injected with 1.0 mL GnRH-A （alarelin） antigen respectively at concentrations of 100, 100 and 50 μg mL-1 respectively, in EG-I, EG-II and EG-III. Alarelin antigen was re-injected in EG-II and EG-III with the same dosage on 20 d. CG was a blank. The ovarian and uterine samples were collected aseptically at the end of the experiment of 70 d. The tissue slices were observed under light and electron microscopes. Serum concentrations of LH and FSH were measured with ELISA. The results showed that serum LH concentrations in EG-II and EG-III reached the peak levels on 50 and 40 d respectively, and LH level in EG-II exceeded other 3 groups on 50 d （P0.05）. FSH level in EG-II was higher than those in EG-I, CG （P0.01） and EG-III （P0.05） on 40 d. GnRH-A could increase the number of primary follicles, enlarge the primary follicle vertical diameter （PFV） and primary follicle transverse diameter （PFT）, and promote growth and maturation of follicles. The endometrial epithelium thickness （EET） and uterine wall thickness （UWT） in three EGs were less than that in CG （P0.05）. GnRH-A can increase the quantities of mitochondrial cristaes, cortex granules in cytoplasm, broaden and lengthen zona pellucidas and microvilli of oocytes. It also enlarged nuclei of ooxytes and mitochondria, thereby it promoted the development of oocytes. Re-injection of 100 μg alarelin antigen enhanced the secretion of LH and FSH. GnRH-A promoted the growth and maturation of ovaries and follicles, suppressed uterine development, and also influenced histostructure of ovaries and uteri in female rabbits.

Clinical efficacy of leprerelin acetate with different dosage forms in central precocious puberty girls

Objective:To observe the clinical efficacy of different dosage forms of lepraline acetate(LA)in the treatment of girls with central precocious puberty(CPP).Methods:72 CPP girls treated in the Department of Pediatrics of Huai'an First People's Hospital from February 2021 to August 2022 were included as subjects and divided into two groups:3-month LA group(n=34)and 1-month LA group(n=38).Both group girls were treated for 6 months.Serum hormone levels,body mass index(BMI),bone age/chronological age(BA/CA)and pelvic color ultrasound were detected at 0 and 6 months after treatment,and the changes of various indexes were compared before and after treatment.Results:1)There were no significant differences in baseline data between the two groups before treatment(P>0.05).2)After 6 months of treatment,BA/CA decreased,growth rate slowed down,and predicted adult height increased in both groups(P<0.05),but there were no significant differences between groups(P>0.05).3)After 6 months of treatment,there waere no significant differences in luteinizing hormone(LH)inhibition ratio between the 3 month and 1 month dosage groups(P>0.05).After treatment,the peak value of serum LH and FSH,estradiol level,uterine volume,bilateral ovarian volume,maximum follicle diameter and the number of follicles 4mm were significantly decreased in the two groups,but there were no significant differences between the two groups(P>0.05).4)There were no significant differences in the levels of thyroid hormone,fasting blood glucose and triglyceride between the two groups before and after treatment(P>0.05).Total cholesterol levels were increased after treatment(P<0.05),but there was no significant difference between groups(P>0.05).5)No serious adverse reactions occurred during the treatment of the two dosage forms of LA,but the 3-month dosage form of LA reduced the treatment cost and improved the treatment compliance.Conclusion:The short-term efficacy of 3-month LA in the treatment of CPP in girls is similar to that of 1-month LA.The 3-month dosage form LA is a safe,effective,and economical method for the treatment of CPP in girls.

Current state and controversies in fertility preservation in women with breast cancer

On average,over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States.Because an increasing number of young women delay childbearing to later life for various reasons,a growing population of women experience breast cancer before completing childbearing.In this context,preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care.In this review,we will outline the currently available fertility preservation options for women with breast cancer of reproductive age,discuss the controversy behind hormonal suppression for gonadal protection against chemotherapy and highlight the importance of timely referral by cancer care providers.

Does Lower Dose of Long-acting Triptorelin Maintain Pituitary Suppression and Produce Good Live Birth Rate in Long Down-regulation Protocol for In-vitro Fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone（Gn RH） agonist in Gn RH agonist long protocol for in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with Gn RH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group（41.2% vs. 43.7%）. The mean luteinizing hormone（LH） level on follicle-stimulating hormone（FSH） starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin（h CG） administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group（12.90±5.82 vs. 13.52±6.97）. There was no significant difference in clinical pregnancy rate between the two groups（50.5% vs. 54.5%）. It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Case Report of Ectopic Pregnancy during Controlled Ovarian Stimulation without Oocytes Harvested and Late Ovarian Hyperstimulation Syndrome

Here we reported a rare case of misdiagnosed ectopic pregnancy (EP) due to unintended ovulation during controlled ovarian stimulation (COS) in GnRH agonist cycle, resulting in no oocytes harvested and late hyper-stimulation syndrome (OHSS). The patient was a 33-year old primary infertile woman due to male’s factors and underwent her second in vitro fertilization (IVF) cycle using GnRH agonist protocol, and no oocytes harvested on ovum picked-up (OPU) day. The start of gonadotropin usage was on day 8th of her period, and the P level increased rapidly and strangely high from day 8th after gonadotropin usage. The E2 level and follicles grew normally but finally no oocytes harvested. She was diagnosed as late ovarian hyper-stimulation syndrome (OHSS) 7 days after OPU. 20 days after OPU, no menstruation come and a positive urine test of hCG were reported. And the patient was diagnosed as EP by laparoscopy. In conclusion, rapidly increased P level, no oocyte retrieval and late onset of OHSS should be very important clues to diagnose this misdiagnosed EP.

Oral Phosphodiesterase Type 5 Inhibitors in Recurrent Priapism Complicating Thalassemia Intermedia: A Case Report

Recurrent priapism is a rare, serious and difficult to treat complication of some hematological disorders, for which no standard therapy exists. This study reports a case of a 42-year-old man with thalassemia intermedia complicated by recurrent episodes of priapism. To prevent priapism recurrences, a trial of PDE5is use was initiated. One day after initiation of a PDE5i (25 mg sildenafil repeated every 8 hours), priapism was improved. For 3 weeks, the patient reported improvement, without experiencing any episodes of priapism and a normal physiologic erectile function. Four weeks after treatment he experienced priapism reoccurrence and doubling of the Sildenafil was not effective. Gonadotropin-releasing hormone agonist initiated and one week after initiatin of new drug he improved. He was free of priapism episodes for more than 2 years afterward. PDE5 deregulation seems to be an underling pathologic mechanism of recurrent priapism at least in thalassemia intermedia patients. It appears that PDE5is may have a role in the management of such patients and further testing in clinical trials is needed.

Different Pretreatments before Application of GnRH Antagonist Protocol in Controlled Ovarian Hyperstimulation

Objective To analyze the clinical features and outcome of patients who used different pretreatments before application of gonadotropin-releasing hormone antagonist protocol during in vitro fertilization - embryo transfer （IVF-ET） cycles, and to explore how effective to use the antagonist protocol. Methods A retrospective analysis was performed. All the ET cycles were divided into three groups, group A （n=125） used short acting GnRH agonist before GnRH antagonist treatment, group B （n=113） used short-acting oral contraceptives before GnRH antagonist treatment, group C （n=81） was untreated before GnRH antagonist treatment. All the patients had no tubal fluid, endometrial polyps and no anatomical abnormalities of the uterus, from April 2010 to December 2010. The patient＇s age, dose and duration of gonadotropin （Gn） treatment, the serum LH and E2 levels on the day of hCG injection, the number of oocytes retrieved, the rates of good-quality embryos, the clinical pregnancy rates were compared. At the same time, 261 GnRH agonist long protocol cycles （group D） were selected at the same period as further comparison. Results The patients in group C （32.9 ~ 4.8 years） were significantly older than those in groups A and B （31.6 ___＋3.7 years, 31.2 ___%4.1 years）（P 〈0.05）. The dose and the duration of Gn in group C were significantly lower than those in groups A and B. The serum LH level on the day of hCG injection in group A and group B was significantly lower than that in group C （P 〈0.05）, especially in group A. The endometrium was the thinnest in group B. There were no significant differences in the fertilization rates and the good-quality embryosrates among them. The clinical pregnancy rate of group B decreased significantly compared with groups A and C （P〈0. 05）. The clinical pregnancy rate of group C was the highest among them. There was no significant difference of clinical pregnancy rates between group C and group D （37% vs 40.2%,P〉0.05）. However, the dose （19.8 ±6.6 ampoule vs 26.4 ±8.1 ampoule） and the duration （9.0± 1.6 d vs 11.6±2.5 d） of Gn treatment in group C were decreased significantly than those in group D, P〈0.05. Conclusion The short acting GnRH agonist used before GnRH antagonist treatment during IVF-ET cycles failed to improve the pregnancy rates, the use of short-acting oral contraceptives before GnRH antagonist treatment makes the pregnancy rates decrease significantly, but untreated before GnRH antagonist protocol can get a better clinical outcome compared with agonist long protocol Untreated GnRH anagonist protocol is the best GnRH anagonist protocol.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.

Chinese Medicine Improves Postoperative Quality of Life in Endometriosis Patients:A Randomized Controlled Trial

Objective： To investigate the effect of Chinese medicine （CM） and Western medicine （WM） on quality of life （QOL） after conservative surgery for endometriosis. Methods： A total of 320 patients with endometdosis were randomized into two groups by using random block design, CM group （160 cases, activating blood circulation and removing blood stasis treatment based on syndrome differentiation） and WM group （160 cases, gonadotropin-releasing hormone agonist or gestrinone treatment） after conservative surgery. Treatment was given for 3-6 months （according to the revised American Fertility Society scoring system stage）, and the Wodd Health Organization QOL-BREF （WHOQOL-BREF） was applied to patients before and after treatment to assess QOL. Results： There were 136 cases in the CM group and 141 cases in the WM group completing therapy. In the CM group, the use of the WHOQOL-BREF showed that the physical, psychological and environmental scores post- treatment were significantly higher than those at pre-treatment （P〈0.05）, and for 12 items （pain and discomfort, energy and fatigue, sleep and rest, mobility, activities of daily living, work capacity, negative feelings, health and social care： accessibility and quality, participation in and opportunities for recreation/leisure activities, appetite, QOL score, overall health status and QOL）, the difference in scores was significant （P〈0.05）. In the WM group, 4 items （pain and discomfort, opportunities for acquiring new information and skills, QOI_ score, overall health status and QOL） had significantly different scores post-treatment compared with those at pre-treatment （P〈0.05）. Before treatment, the QOL in the two groups of patients showed no significant difference （P〉0.05）. After treatment, the scores for physical health in the CM group were significantly higher than those of the WM group （P〈0.05） and the scores of 4 items （mobility, activities of daily living, sexual activity, QOL score） in the CM group were significantly higher than those in the WM group （P〈0.05）. Conclusions： CM and WM treatment could improve the QOL of patients with endometriosis after conservative surgery. CM treatment is more effective than WM.