Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome:A case report and review of the literature

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes.It is characterized by a deficiency in anterior pituitary hormones,such as growth hormone,gonadotropins,and thyroid hormones.Due to the syndrome's rarity and nonspecific manifestations,there is a lack of standardized treatment strategies.Consequently,early diagnosis through imaging and on-time intervention are crucial for improving patients’outcomes.CASE SUMMARY A 30-year-old man presented with absent secondary sexual characteristics and azoospermia.Laboratory evaluation revealed a deficiency in gonadotropins,while thyroid function was mostly within normal ranges.Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis,hypoplasia of the anterior pituitary,and ectopic posterior pituitary,leading to the diagnosis of PSIS.Initially,the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics.Pulsatile gonadotropin-releasing hormone therapy was then administered,resulting in the detection of sperm in the semen analysis within 3 mo.After 6 mo,routine semen tests showed normal semen quality.The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination,which was unsuccessful.They also attempted in vitro fertilization,but unfortunately,the woman experienced a miscarriage 10 wk after the embryo transfer.CONCLUSION Early detection,accurate diagnosis,and timely treatment are crucial in improving the quality of life and fertility of PSIS patients.

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.

Immunohistochemical Localization and Receptor Expression of Gonadotropin-Releasing Hormone in Pituitary of Guangxi Swamp Buffaloes

[ Objective] To locate gonadotropin-releasing hormone （GnRH） in pituitary of Guangxi swamp buffaloes and to provide a theoretical ba- sis for cloning and sequence analysis of GnRH receptor gene. [ Method] GnRH in pituitary were immunohistochemically stained by avidin biotin complex method. The GnRH expression was analyzed with image system. The GnRH receptor gene was amplified by real-time PCR. [ Result] Many GnRH positive cells were detected in pars distalis of adenohypophysis. GnRH were distributed in cytoplasm but not in nuclei. No positive sig- nal was observed in neurohypophysis. In addition, the GnRH receptor gene, 920 bp in size, was amplified. [ Conclusion] A large number of GnRH and GnRH receptor were found in pars distalis of adenohypophysis, which indicates that anterior pituitary is an important tissue for functions of hypo- thalamus-pituitary-gonadal axis and other endocrine axes.

Associations of Gonadotropin-Releasing Hormone Receptor (GnRHR) and Neuropeptide Y(NPY) Genes’Polymorphisms with Egg-Laying Traits in Wenchang Chicken

Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of Wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.

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.

Identification and distribution of gonadotropin-releasing hormone-like peptides in the brain of horseshoe crab Tachypleus tridentatus

Gonadotropin-releasing hormone （GnRH） is a crucial peptide for the regulation of reproduction. Using immunological techniques, we investigated the presence of GnRH in horseshoe crab Tachypleus tridentatus. Octopus GnRH-like immunoreactivity, tunicate GnRH-like immunoreactivity, and lamprey GnRH-I-like immunoreactivity were detected in the neurons and fibers of the protocerebrum. However, no mammal GnRH-like immunoreactivity or lamprey GnRH-LII-like immunoreactivity was observed. Our results suggest that a GnRH-like factor, an ancient peptide, existed in the brain of T. tridentatus and may be involved in the reproductive endocrine system.

Morphological changes of gonadotropin-releasing hormone neurons in the rat preoptic area across puberty

Gonadotropin-releasing hormone （GnRH） neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons.

Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels （at 120 minutes of exposure） and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

Changes in Electrocardiogram Findings during Treatment with Gonadotropin-Releasing Hormone Agonist and Surgical Castration for Prostate Carcinoma

Purpose: To investigate electrocardiogram (ECG) changes after complete androgen blockade (CAB) achieved by either surgical or medical castration and compare the outcomes of the groups. Methods: Sixty-three consecutive men (between 58 - 86 years of age) requiring CAB for prostate cancer were enrolled in the study. Patients with diabetes mellitus, an additional malignancy, coronary heart disease, atrial fibrillation, heart failure or a medical history of cardiac event in the last 12 months were excluded from the study. Additionally, those who were taking medicine affecting heart rate were excluded. The participants were divided into two groups according to their modality of castration. The first group consisted of 35 patients who received bilateral orchiectomy plus anti-androgen medication. The second group contained 28 patients who accepted gonadotropin-releasing hormone (GnRH) plus anti-androgen therapy. After complete examinations and biochemical tests, the ECG leads of the patients were obtained conveniently. This was then repeated at three- and six-month visits. ECG findings (including heart rate, PR, QRS, QT, corrected QT (QTc) intervals and QT dispersion (QTd)) were recorded and analysed statistically. The groups were then compared in terms of pre- and post-treatment ECG outcomes. Results: Both groups revealed similarly lower heart rate and prolonged PR, QRS, QT, corrected QTc and QTd by the end of six months. By the end of three months, all variables had changed significantly in the orchiectomy group, whereas in the GnRH group, they had not. Conclusion: CAB may result in lower heart rate and prolonged QT, a condition associated with fatal cardiac arrhythmia and sudden death. Therefore, patients receiving CAB should be monitored closely for cardiac adverse effects.

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.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve

Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.

Association between luteinizing hormone level decrease on the triggering day and pregnancy outcome for in vitro fertilization/intracytoplasmic sperm injection patients following gonadotropin-releasing hormone antagonist protocol: a retrospective cohor

Objective:Optimal luteinizing hormone(LH)levels forin vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)patients following the gonadotropin-releasing hormone(GnRH)antagonist protocol remain controversial.This study aimed to estimate the association between serum LH levels on the triggering day(LHLOT)and clinical pregnancy outcomes in IVF/ICSI patients following the GnRH antagonist protocol.Methods:We enrolled 4743 IVF/ICSI cycles using flexible or fixed GnRH antagonist protocols between January 2017 and June 2021.The patients were stratified into four groups according to the LHLOT quartiles(Q1–Q4).Each group was further divided into two subgroups according to the median basal LH/LHLOT.The main outcomes were clinical pregnancy,birth,and miscarriage rates.Secondary outcomes were oocyte yield,number of MII,fertilized oocytes(2PN),and high-quality embryos.Results:Serum LHLOT levels were negatively correlated with oocyte yield and the numbers of MII,2PN,and high-quality embryos.Reproductive outcomes were compared among the different quartiles and subgroups.The absolute difference in the clinical pregnancy rates between the Q4 and Q1 groups was 6.4%(47.2%vs.40.8%,P<0.05).Clinical pregnancy rates between the subgroups with basal LH/LHLOT>3.04 and≤3.04 were 32.7%and 48.6%(P<0.01),respectively,in Q1.Within Q3,the clinical pregnancy rates between the subgroups with basal LH/LHLOT>2.14 and≤2.14 were 50.2%and 41.9%,respectively(P<0.05).The greater the decrease in LH levels,the lower the oocyte maturation rate across all quartiles.Conclusions:According to the LHLOT quartiles,the Q1 of serum LHLOT<1.43 IU/L may result in a higher number of oocytes but reduced oocyte maturation and lower clinical pregnancy rates.A decrease in LH levels by approximately 2.14 to 3.04 times compared to basal LH levels may lead to higher clinical pregnancy rates in IVF/ICSI patients following the GnRH antagonist protocol.

Impact of gonadotropin-releasing hormone agonist and hormone replacement therapy on pregnancy outcomes in single euploid frozen-thawed embryo transfer for patients with endometrial polyps

Objective:Although consensus on the optimal endometrial preparation protocol for frozen-thawed embryo transfer(FET)is lacking,this is particularly true for patients with infertility and a history of endometrial polyps(EPs).In this study,we aimed to investigate whether a gonadotropin-releasing hormone agonist combined with hormone replacement therapy(GnRHa-HRT)could improve pregnancy outcomes in single euploid FET for patients with a history of EPs.Methods:In this retrospective cohort study,395 women who underwent their first single euploid FET cycle were divided into groups according to endometrial preparation protocols as follows:natural cycle(NC)(n=220),hormone replacement therapy(HRT)(n=122),and GnRHa-HRT groups(n=53).Subsequently,the FET cycles in the three groups were subdivided according to maternal age.All patients underwent hysteroscopic polypectomy before FET,and their EPs were confirmed by pathology.Results:No statistically significant differences were observed in live birth rates among the three groups(58.64%vs.58.20%vs.56.60%,P=0.964).Furthermore,the rates of miscarriage,ectopic pregnancy,premature live birth,and pregnancy complications were comparable among the three groups(P>0.05).After adjusting for potential confounding factors,no significant differences in pregnancy outcomes were reported between the groups(adjusted odds ratios[OR]and 95%credible intervals[CI]for live birth rate,HRTvs.NC:1.119,0.660–1.896,P=0.677;GnRHa-HRTvs.NC:1.165,0.610–2.226,P=0.643).Additionally,the pregnancy outcomes of the FET cycle were not influenced by the endometrial preparation protocols in the subgroups when stratified by maternal age(P>0.05).Conclusion:GnRHa-HRT did not improve the pregnancy outcomes of the single euploid FET in patients with a history of EPs.

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.

Comparison of Vaginal Gel and Intramuscular Progesterone for In vitro Fertilization and Embryo Transfer with Gonadotropin-Releasing Hormone Antagonist Protocol

Background： Luteal support is a key to patients undergoing in vitro fertilization and embryo transfer （IVF-ET） with gonadotropin-releasing hormone （GnRH）-antagonist protocol. This study aimed to compare the effect between vaginal progesterone （VP） and intramuscular progesterone （IMP） with GnRH-antagonist protocol alter IVF-ET. Methods： A total of 1760 patients （18 years ≤ age ≤35 years） undergoing IVF-ET with GnRH-antagonist protocol were studied retrospectively between September 2014 and August 2015 in Peking University Third Hospital. In the patients, 1341 patients received VP （VP group） and 419 patients received IMP （IMP group） as luteal support. We compared clinical outcomes between these two groups. The primary objective of the study was the live birth rate. Measurement data between the two groups were conducted using independent samples t-test. The variables in line with non-normal distribution were expressed as median （p25 and p75） and were compared using nonparametric Mann. Whitney U-test. Results： Live birth rate in VP group was 38.55%, significantly higher than that in the IMP group, which was 30.79% （x^2 = 8.287, P= 0.004）. The clinical intrauterine pregnancy rate and implantation rate in VP group were also significantly higher than those in the IMP group （clinical intrauterine pregnancy rate 47.35% vs. 41.29%, x^2= 4.727, P = 0.030： implantation rate 30.99% vs. 25.26%, x^2=14.546, P 〈 0.001）. Any statistically significant differences in ectopic pregnancy and abortion rates between two groups were not observed. Conclusion： Luteal support with VP had better clinical outcomes for young women undergoing IVF-ET with GnRH-antagonist protocol.

Efficacy and safety of human chorionic gonadotropin combined with human menopausal gonadotropin and a gonadotropin-releasing hormone pump for male adolescents with congenital hypogonadotropic hypogonadism

Background:Compared to adult studies,studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism(CHH)are limited and no universal treatment regimen is available.The aim of this study was to evaluate the feasibility of human chorionic gonadotropin(hCG)/human menopausal gonadotropin(hMG)therapy for treating male adolescents with CHH.Methods:Male adolescent CHH patients were treated with hCG/hMG(n=20)or a gonadotropin-releasing hormone(GnRH)pump(n=21).The treatment was divided into a study phase(0-3 months)and a follow-up phase(3-12 months).The testicular volume(TV),penile length(PL),penis diameter(PD),and sex hormone levels were compared between the two groups.The TV and other indicators between the groups were analyzed using a t-test(equal variance)or a rank sum test(unequal variance).Results:Before treatment,there was no statistical difference between the two groups in terms of the biochemistry,hormones,and other demographic indicators.After 3 months of treatment,the TV of the hCG/hMG and GnRH groups increased to 5.1±2.3 mL and 4.1±1.8 mL,respectively;however,the difference was not statistically significant(P>0.05,t=1.394).The PL reached 6.9±1.8 cm and 5.1±1.6 cm(P<0.05,t=3.083),the PD reached 2.4±0.5 cm and 2.0±0.6 cm(P<0.05,t=2.224),respectively,in the two groups.At the end of 6 months of treatment,biomarkers were in normal range in the two groups.Compared with the GnRH group,the testosterone(T)level and growth of PL and PD were significantly greater in the hCG/hMG group(all P<0.05).While the TV of both groups increased,the difference was not statistically significant(P>0.05,t=0.314).After 9 to 12 months of treatment,the T level was higher in the hCG/hMG group.Other parameters did not exhibit a statistical difference.Conclusions:The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH.The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy.Furthermore,results from the extended time-period showed positive outcomes at the 1-year mark;however,the long-term effectiveness,strengths,and weaknesses of the hCG/hMG regimen require further research.Trial Registration:ClinicalTrials.gov,NCT02880280;https://clinicaltrials.gov/ct2/show/NCT02880280.