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.

Gonadotropin releasing hormone agonists and laparoscopy in the treatment of adenomyosis with infertility

To study the role and value of gonadotropin releasing hormone agonists (GnRH a) and laparoscopy for the treatment of adenomyosis with infertility Methods Four cases were seen with adenomyosis and infertility, 3 of these cases also presented local adenomyomata in the posterior uterine wall GnRH a Triptorelin (decapeptyl) or Goserelin (Zoladex) therapy was instituted for six months before laqaroscopic surgery for coexisting pelvic pathologic infertility factors in one case and after laparoscopic surgery in three cases Results All cases remained amenorrheic during GnRH a therapy After the GnRH a therapy, all enlarged uterus (7-10 weeks gestation size) all decreased to normal or near normal size; menstruation returned in 80-90 days and three cases conceived within four menstrual periods after cessation of treatment In the 4 cases one pregnancy resulted in the birth of a healthy 3150?g male newborn at 38 weeks gestation by cesarean section; one pregnancy was terminated after adenomyomectomy by emergency cesarean section at 30 weeks gestation because of threatened rupture of uterus; one case was then normal at 28 weeks pregnancy; the last case had 2 resumptive menstrual periods and was still being followed up Conclusions GnRH a is markedly efficient in reducing adenomyotic uterine size, facilitates uterine or endometrial receptivity for embryos and enhances uterine ability to maintain pregnancy For adenomyomata associated with infertility, GnRH a instead of surgical removal of lesions, which are deep in the myometrium, may avoid uterine rupture when pregnancy occurs For infertility, GnRH a treatment before laparoscopic surgery greatly decreases surgical difficulties and blood loss in certain cases

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.

Intracerebroventricular leptin injection affects neuroendocrine reproductive axis in ovariectomized rats

BACKGROUND：Leptin regulates neuroendocrine function of the hypothalamus-pituitary-ovary axis in humans. OBJECTIVE： To verify effects of intracerebroventricular leptin injection on neuroendocrine function of the hypothalamus-pituitary-ovary axis in ovariectomized rats. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Basic Medical Institute, Chengde Medical College between June and October 2007. MATERIALS： Thirty healthy, female, Wistar rats were included in this study. The following compounds were used： leptin; gonadotropin-releasing hormone （GnRH） and luteinizing hormone （LH） enzyme-linked immunosorbent assay kits. METHODS： Rats were randomly divided into 3 groups at 1, 2, and 4 hours after injection. Each group was subdivided into control and experimental groups （n = 5 animals per group and time point）. All rats were subjected to bilateral ovariectomy and, beginning on day 7 after surgery, animals received daily subcutaneous injections of estradiol benzoate （2 μg） for 7 consecutive days. The experimental groups were injected with 5 μL leptin （1 g/L） into the lateral cerebral ventricle, and control groups received an equal volume of physiological saline. MAIN OUTCOME MEASURES： GnRH and LH secretion were examined 1, 2, and 4 hours after injection using GnRH and LH ELISA kits, respectively. RESULTS： In the experimental groups, GnRH secretion significantly increased （P 〈 0.01）, followed by LH secretion （P 〈 0.01）, compared with the control groups. GnRH secretion significantly increased 1 hour after leptin injection （P 〈 0.01）. The LH increase was less pronounced, but still significant （P 〈 0.01）; however, the most prominent LH increase occurred between 1 and 2 hours. Both GnRH and LH secretion reached peak levels at 2 hours after leptin injection. Thereafter, both GnRH and LH secretion decreased, but still maintained very high levels, compared with the control group （P 〈 0.01）. CONCLUSION： Intracerebroventricular leptin injection produced similar effects on GnRH and LH secretion in ovariectomized rats, indicating regulatory effects of leptin on GnRH and LH secretion.

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze-all strategy: A case report and review of the literature

Rationale:The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin(hCG)for luteal support as an explanation for the development of ovarian hyperstimulation syndrome,and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome.Patient concerns:A case of 25-year-old woman presented with abdominal pain,distention,dyspnea,and nausea with a 6.5 kg increase in weight from baseline.Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone(GnRH)agonist triggering and cycle segmentation with no hCG rescue administration.Diagnosis:Moderate/severe ovarian hyperstimulation syndrome.Interventions:The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome,and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin.On day 2,albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth.On day 1,Cabergoline was maintained,and on day 2 the GnRH antagonist Cetrorelix was started.Outcomes:The woman’s clinical condition improved,and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle.Lessons:Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support.Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.

COLOCALIZATION OF NITRIC OXIDE SYNTHASE IN GNRH NEURONS OF RAT FOREBRAIN AND HYPOTHALAMUS

In order to gain more information about the effect of nitric oxide (NO) on GnRH release, double NADPH diaphorase histochemistry GnRH immunohistochemistry staining was used to investigate the morphological relationship between NO synthase (NOS) containing cells and GnRH neurons in the forebrain and hypothalamus of rats. The results showed that some of the GnRH neurons in the diagonal band of Broca, olfactory tubercle and deeper part of temporal cortex had the NOS activity, suggesting GnRH secretion can be rapidly regulated by NO derived from GnRH neurons themselves in an autocrine manner.

A classification of genes involved in normal and delayed male puberty

Puberty is a pivotal biological process that completes sexual maturation to achieve full reproductive capability.It is a major transformational period of life,whose timing is strongly affected by genetic makeup of the individual,along with various internal and external factors.Although the exact mechanism for initiation of the cascade of molecular events that culminate in puberty is not yet known,the process of pubertal onset involves interaction of numerous complex signaling pathways of hypothalamopituitary-testicular(HPT)axis.We developed a classification of the mechanisms involved in male puberty that allowed placing many genes into physiological context.These include(i)hypothalamic development during embryogenesis,(ii)synaptogenesis where gonadotropin releasing hormone(GnRH)neurons form neuronal connections with suprahypothalamic neurons,(iii)maintenance of neuron homeostasis,(iv)regulation of synthesis and secretion of GnRH,(v)appropriate receptors/proteins on neurons governing GnRH production and release,(vi)signaling molecules activated by the receptors,(vii)the synthesis and release of GnRH,(viii)the production and release of gonadotropins,(ix)testicular development,(x)synthesis and release of steroid hormones from testes,and(xi)the action of steroid hormones in downstream effector tissues.Defects in components of this system during embryonic development,childhood/adolescence,or adulthood may disrupt/nullify puberty,leading to long-term male infertility and/or hypogonadism.This review provides a list of 598 genes involved in the development of HPT axis and classified according to this schema.Furthermore,this review identifies a subset of 75 genes for which genetic mutations are reported to delay or disrupt male puberty.

Effect of preopera tivetranscatheter arterial chemoembolization on tumor cell activity in hepatocellular carcinoma

To study the role and value of gonadotropin releasing hormone agonists (GnRH a) and laparoscopy for the treatment of adenomyosis with infertility Methods Four cases were seen with adenomyosis and infertility, 3 of these cases also presented local adenomyomata in the posterior uterine wall GnRH a Triptorelin (decapeptyl) or Goserelin (Zoladex) therapy was instituted for six months before laqaroscopic surgery for coexisting pelvic pathologic infertility factors in one case and after laparoscopic surgery in three cases Results All cases remained amenorrheic during GnRH a therapy After the GnRH a therapy, all enlarged uterus (7-10 weeks gestation size) all decreased to normal or near normal size; menstruation returned in 80-90 days and three cases conceived within four menstrual periods after cessation of treatment In the 4 cases one pregnancy resulted in the birth of a healthy 3150?g male newborn at 38 weeks gestation by cesarean section; one pregnancy was terminated after adenomyomectomy by emergency cesarean section at 30 weeks gestation because of threatened rupture of uterus; one case was then normal at 28 weeks pregnancy; the last case had 2 resumptive menstrual periods and was still being followed up Conclusions GnRH a is markedly efficient in reducing adenomyotic uterine size, facilitates uterine or endometrial receptivity for embryos and enhances uterine ability to maintain pregnancy For adenomyomata associated with infertility, GnRH a instead of surgical removal of lesions, which are deep in the myometrium, may avoid uterine rupture when pregnancy occurs For infertility, GnRH a treatment before laparoscopic surgery greatly decreases surgical difficulties and blood loss in certain cases