Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizi...Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizing hormone(LH)were identified the key elements of the HPG axis in teleost and mammal.Morphology,cell lines,and gonadotropins cell localization of female turbot and mouse pituitary were determined at mature stage to illustrate the anatomical difference and cell characteristics in this study.Results show that turbot pituitary is chicken heart-shaped,dorsoventral,located on the ventral surface of the diencephalon.The mouse pituitary is oval,located in the pituitary fossa of the sella turcica at the skull base.Two well-distinguished areas adenohypophysis(AH)and neurohypophysis(NH)in pituitary were identified in turbot and mouse.Turbot AH comprised the rostral pars distalis(RPD),proximal pars distalis(PPD),and pars intermedia(PI).NH was not pronounced and with finger-like protrusions into PPD.However,mouse AH only comprised the pars distalis(PD)and PI.NH distribution was semicircular.Three main types of cells(acidophilic,basophilic,and chromophobic cells)were distributed in the mouse PD region,whereas appeared in the turbot PPD,RPD,and PI.Moreover,the percentage of mouse chromophobic and basophilic cells was higher and lower than that of turbot,respectively.The diameter of the aforementioned three cells in the mouse was significantly higher than turbot.fshβ-and lhβ-immunoreactive signals were identified in turbot-distinct pituitary cells that primarily occupied the peripheral and central regions of AH.However,mouse fsh-and lh-immunoreactive cells were expressed in the same cells and present in the PD.These results demonstrate the significantly difference of pituitary morphology,cell lines and gonadotropins(fshβand lhβ)location in female turbot and mouse.These differences help for fully understand the evolution and endocrinological functions of pituitary.展开更多
Gon adotropin therapy is comm only used to in duce virilizati on and spermatoge nesis in male isolated hypog on adotropic hypog on adism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor ...Gon adotropin therapy is comm only used to in duce virilizati on and spermatoge nesis in male isolated hypog on adotropic hypog on adism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment;therefore, testosterone (T) suppleme ntation can serve as an alter native therapy to no rmalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undeca noate (TU) suppleme ntation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) mon ths in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.展开更多
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 ...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.展开更多
To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IV...To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IVF/ICSI and the subsequent pregnancy outcome in frozen-thawed embryo transfer （FET）. Methods In the retrospective cohort study, 2 166patients undergoing IVF/ICSI with moderate or high response were recruited and classified into three groups according to the trigger dose of hCG： 2 000 IU （group A, n=722）, 3 000 IU （group B, n=722） and 5 000 IU （group C, n= 722）. The main outcome was the proportion of mature oocytes retrieved, fertilization rates, clinical pregnancy rates, cumulative pregnancy rates and incidence of ovarian hyperstimulation syndrome （OHSS）. Results No evidence of statistically difference was found in the proportion of mature oocytes retrieved （89.92%, 91.40%, 90.20%, respectively） and fertilization rate （79.8%, 80.07%, 80.51%, respectively） among groups A, B and C. Serum E2 level on the day of hCG injection, the number of mature oocytes retrieved and good-quality embryos in group A were significantly higher than those in group B and group C. Clinical pregnancy rates per transfer cycle （45.95%, 43.97% and 44.25%）, ongoing pregnancy rates （43.17%, 40.91% and 42,53%）, implantation rates （30, 74%, 2Z 78% and 29.86%） and cumulative pregnancy rates per patient （58.31%, 53.6% and 54.85%）A reduced hCG dose of 2 000 IUfor moderate or high responders leads展开更多
Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathog...Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.展开更多
Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the po...Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.展开更多
Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple o...Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.展开更多
Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with...Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with medical therapy in 3 quarters of cases.There are forms of congenital HH,whether or not associated with an absent sense of smell(anosmic HH or Kallmann syndrome,and normosmic HH,respectively),and forms of acquired HH.In congenital HH,complete absence of pubertal development is characteristic.On the other hand,if the deficit occurs after the time of pubertal development,as in acquired HH patients,infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance.Gonadotropin-releasing hormone(GnRH)or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results,although a small but significant proportion of patients do not achieve sufficient responses.展开更多
Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice...Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.展开更多
BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,wh...BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,which leads to insufficient understanding by clinicians,misdiagnosis,and unnecessary surgeries.CASE SUMMARY A 22-year-old female patient presented with bloody stool and elevated human chorionic gonadotropin.The transvaginal gynecological ultrasound ruled out pregnancy.Upper gastrointestinal endoscopy and colonoscopy were performed,but no bleeding focus was detected.The contrast-enhanced computed tomography was unremarkable.The capsule endoscopy suggested jejunal protuberant lesions with dark red blood clots.Therefore,oral single-balloon enteroscopy was performed,and two connected protuberant lesions were detected,with blood clot traces and local ulceration.The enteroscopic biopsy revealed trophoblastic cells with a probable diagnosis of trophoblastic tumor.The patient underwent surgical resection of the diseased jejunum.Intraoperative endoscopy was performed,and the findings were the same as those of the small intestine endoscopy.The postoperative pathology confirmed the preoperative diagnosis of invasive mole.CONCLUSION In non-pregnant women with elevated human chorionic gonadotropin and gastrointestinal bleeding,metastatic trophoblastic neoplasia should be considered.展开更多
This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; the...This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.展开更多
Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can ...Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators （clomiphene）, estrogen conversion blockers （anastrozole）, and hormone replacement.展开更多
Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ET...Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.展开更多
Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in...Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.展开更多
基金Supported by the National Natural Science Foundation of China(No.31972811)the Special Fund for Basic Scientific Research of Central Public Research Institutes(No.2020T51)。
文摘Reproduction is subtlety regulated by the hypothalamic-pituitary-gonad(HPG)axis in vertebrates.Pituitary gland is the center of the HPG axis,while pituitary gonadotropins follicle stimulating hormone(FSH)and luteinizing hormone(LH)were identified the key elements of the HPG axis in teleost and mammal.Morphology,cell lines,and gonadotropins cell localization of female turbot and mouse pituitary were determined at mature stage to illustrate the anatomical difference and cell characteristics in this study.Results show that turbot pituitary is chicken heart-shaped,dorsoventral,located on the ventral surface of the diencephalon.The mouse pituitary is oval,located in the pituitary fossa of the sella turcica at the skull base.Two well-distinguished areas adenohypophysis(AH)and neurohypophysis(NH)in pituitary were identified in turbot and mouse.Turbot AH comprised the rostral pars distalis(RPD),proximal pars distalis(PPD),and pars intermedia(PI).NH was not pronounced and with finger-like protrusions into PPD.However,mouse AH only comprised the pars distalis(PD)and PI.NH distribution was semicircular.Three main types of cells(acidophilic,basophilic,and chromophobic cells)were distributed in the mouse PD region,whereas appeared in the turbot PPD,RPD,and PI.Moreover,the percentage of mouse chromophobic and basophilic cells was higher and lower than that of turbot,respectively.The diameter of the aforementioned three cells in the mouse was significantly higher than turbot.fshβ-and lhβ-immunoreactive signals were identified in turbot-distinct pituitary cells that primarily occupied the peripheral and central regions of AH.However,mouse fsh-and lh-immunoreactive cells were expressed in the same cells and present in the PD.These results demonstrate the significantly difference of pituitary morphology,cell lines and gonadotropins(fshβand lhβ)location in female turbot and mouse.These differences help for fully understand the evolution and endocrinological functions of pituitary.
基金the grant from the National Natural Science Foundation of China (Project No. 81671443, 81601270).
文摘Gon adotropin therapy is comm only used to in duce virilizati on and spermatoge nesis in male isolated hypog on adotropic hypog on adism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment;therefore, testosterone (T) suppleme ntation can serve as an alter native therapy to no rmalize serum T levels and promote virilization. However, treatment with exogenous T impairs spermatogenesis and suppresses intratesticular T levels. This retrospective study aimed to determine whether oral testosterone undeca noate (TU) suppleme ntation together with human chorionic gonadotropin (hCG) would negatively affect spermatogenesis in IHH patients compared with hCG alone. One hundred and seven IHH patients were included in our study. Fifty-four patients received intramuscular hCG and oral TU, and 53 patients received intramuscular hCG alone. The median follow-up time was 29 (range: 12-72) mon ths in both groups. Compared with the hCG group, the hCG/TU group required a shorter median time to normalize serum T levels (P < 0.001) and achieve Tanner stage (III and V) of pubic hair and genital development (P < 0.05). However, there were no significant differences in the rate of seminal spermatozoa appearance, sperm concentration, or median time to achieve different sperm concentration thresholds between the groups. In addition, there were no significant differences in side effects, such as acne and gynecomastia, observed in both groups. This study indicates that oral TU supplementation together with hCG does not impair spermatogenesis in treated IHH patients compared with hCG alone, and it shortens the time to normalize serum T levels and promote virilization.
文摘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.
基金supported by National Natural Science Foundation of China(No.31071275)Natural Science Foundation of Shanghai of China(No.09411962900)
文摘To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IVF/ICSI and the subsequent pregnancy outcome in frozen-thawed embryo transfer （FET）. Methods In the retrospective cohort study, 2 166patients undergoing IVF/ICSI with moderate or high response were recruited and classified into three groups according to the trigger dose of hCG： 2 000 IU （group A, n=722）, 3 000 IU （group B, n=722） and 5 000 IU （group C, n= 722）. The main outcome was the proportion of mature oocytes retrieved, fertilization rates, clinical pregnancy rates, cumulative pregnancy rates and incidence of ovarian hyperstimulation syndrome （OHSS）. Results No evidence of statistically difference was found in the proportion of mature oocytes retrieved （89.92%, 91.40%, 90.20%, respectively） and fertilization rate （79.8%, 80.07%, 80.51%, respectively） among groups A, B and C. Serum E2 level on the day of hCG injection, the number of mature oocytes retrieved and good-quality embryos in group A were significantly higher than those in group B and group C. Clinical pregnancy rates per transfer cycle （45.95%, 43.97% and 44.25%）, ongoing pregnancy rates （43.17%, 40.91% and 42,53%）, implantation rates （30, 74%, 2Z 78% and 29.86%） and cumulative pregnancy rates per patient （58.31%, 53.6% and 54.85%）A reduced hCG dose of 2 000 IUfor moderate or high responders leads
文摘Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.
文摘Except in cases of hypogonadotropic hypogonadism,the use of medical therapy before microsurgical testicular sperm extraction(micro-TESE)is controversial.In some studies,hormone therapy has been shown to improve the possibility of sperm retrieval during micro-TESE and even lead to the presence of sperm in the ejaculate in some cases,thereby obviating the need for micro-TESE.However,their routine use before micro-TESE in cases of nonobstructive azoospermia(NOA)being associated with hypergonadotropic hypogonadism and eugonadism(normogonadotropic condition)has not been supported with robust evidence.In this review,we discuss different types of medical therapy used before micro-TESE for NOA,their risks and benefits,and the available evidence surrounding their use in this setting.
基金National Natural Science Foundation of China(31930103)National Center of Technology Innovation for Pigs(NCTIP-XD/B03)+2 种基金Ningbo Major Science and Technology Project(2021Z112)National Key R&D Program(2022YFD1300303)Beijing Innovation Consortium of Livestock Research System BAIC05-2024.
文摘Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.
文摘Hypogonadotropic hypogonadism(HH)represents a relatively rare cause of nonobstructive azoospermia(NOA),but its knowledge is crucial for the clinical andrologists,as it represents a condition that can be corrected with medical therapy in 3 quarters of cases.There are forms of congenital HH,whether or not associated with an absent sense of smell(anosmic HH or Kallmann syndrome,and normosmic HH,respectively),and forms of acquired HH.In congenital HH,complete absence of pubertal development is characteristic.On the other hand,if the deficit occurs after the time of pubertal development,as in acquired HH patients,infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance.Gonadotropin-releasing hormone(GnRH)or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results,although a small but significant proportion of patients do not achieve sufficient responses.
基金National Natural Science Foundation of China,Grant/Award Number:82101937Guangdong Medical Science and Technology Research Fund Project,China,Grant/Award Number:B2024069Guangzhou Science and Technology Plan Project,China,Grant/Award Number:2024A04J4923 and SL2023A04J02229。
文摘Background:Makorin ring finger protein 3 gene(MKRN3)gene mutation is the most common genetic cause of central precocious puberty(CPP)in children.Due to the lack of ideal MKRN3-modified animal model(MKRN3-modified mice enter puberty only 4–5 days earlier than normal mice),the related research is limited.Methods:Therefore,the MKRN3-modified rabbit was developed using CRISPR(clus-tered regularly interspaced short palindromic repeats)gene editing technology.The genotype identification and phenotype evaluation of MKRN3-modified rabbits were carried out.Results:The first estrus of MKRN3-modified female rabbits was observed~27 days earlier than that of wild-type female rabbits,with a typical CPP phenotype.This study found increased gonadotropin releasing hormone(GnRH)and decreased gonadotropin inhibiting hormone(GnIH)in the hypothalamus of the CPP rabbit model with MKRN3 gene mutation.Although this study failed to fully clarify the pathogenesis of CPP caused by MKRN3 mutation,it found some differentially expressed genes and potential pathways through transcriptome sequencing.Conclusions:This study established a novel CPP model:paternal MKRN3 gene-modified rabbit.It is hoped that the establishment of this model will help researchers better understand,treat,and prevent CPP in the future.
文摘BACKGROUND Gastrointestinal bleeding due to metastasis of an invasive mole to the small intestine is very rare.Most reported cases of metastatic invasive mole are diagnosed after surgery,and lack rich illustrations,which leads to insufficient understanding by clinicians,misdiagnosis,and unnecessary surgeries.CASE SUMMARY A 22-year-old female patient presented with bloody stool and elevated human chorionic gonadotropin.The transvaginal gynecological ultrasound ruled out pregnancy.Upper gastrointestinal endoscopy and colonoscopy were performed,but no bleeding focus was detected.The contrast-enhanced computed tomography was unremarkable.The capsule endoscopy suggested jejunal protuberant lesions with dark red blood clots.Therefore,oral single-balloon enteroscopy was performed,and two connected protuberant lesions were detected,with blood clot traces and local ulceration.The enteroscopic biopsy revealed trophoblastic cells with a probable diagnosis of trophoblastic tumor.The patient underwent surgical resection of the diseased jejunum.Intraoperative endoscopy was performed,and the findings were the same as those of the small intestine endoscopy.The postoperative pathology confirmed the preoperative diagnosis of invasive mole.CONCLUSION In non-pregnant women with elevated human chorionic gonadotropin and gastrointestinal bleeding,metastatic trophoblastic neoplasia should be considered.
文摘This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.
文摘Male factor contributes to 50%-60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators （clomiphene）, estrogen conversion blockers （anastrozole）, and hormone replacement.
文摘Gestational trophoblastic neoplasia(GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma(CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor(PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases.The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics(FIGO)2000 criteria: four or more plateaued human chorionic gonadotropin(hCG)concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However,the latter reason for treatment is no longer used by many centers. In addition,GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate(MTX) or Actinomycin-D(Act-D), can cure about 70% of patients with FIGO/World Health Organization(WHO) prognosis risk score ≤ 6(low risk), reserving multiple agent chemotherapy, such as EMA/CO(Etoposide,MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7(high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death,allow the healing and maintenance of the reproductive potential of these women.
文摘Both pulsatile gonadotropin-releasing hormone （GnRH） infusion and combined gonadotropin therapy （human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]） are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism （CH H）. However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH： twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months （range： 12-27 months） for the GnRH group and 28.7 ± 13.0 months （range： 12-66 months） for the HCG/HMG group. The median time to first sperm appearance was 6 months （95% confidence interval [CI]： 1.6-10.4） in the GnRH group versus 18 months （95% Ch 16.4-20.0） in the HCG/HMG group （P〈 0.001）. The median time to achieve sperm concentrations 〉5 x 106 m1-1 was 14 months （95% Ch 5.8-22.2） in the GnRH group versus 27 months （95% Ch 18.9-35.1） in the HCG/HMG group （P 〈 0.001）, and the median time to concentrations 〉10 x 106 m1-1 was 18 months （95% Ch 10.0-26.0） in the GnRH group versus 39 months （95% CI unknown） in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of 〉4 ml, 〉8 ml, 〉12 ml, and 〉16 ml. Sperm motility （a ＋ b ＋ c percentage） evaluated in semen samples with concentrations 〉1 × 106 ml-1 was 43.7% ± 20.4% （16 samples） in the GnRH group versus 43.2% ± 18.1% （153 samples） in the HCG/HMG group （P= 0.921）. Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group （8.3 ±4.6 vs 16.2 ± 8.2 nmol 1-1, P 〈 0.001）. Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.
