Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.
Adolescent ; Adult ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Gonadotropins/therapeutic use* ; Hormone Replacement Therapy/methods* ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/therapeutic use* ; Male ; Middle Aged ; Retrospective Studies ; Spermatogenesis/drug effects* ; Young Adult

The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years), a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.
Age Factors ; Androgens/therapeutic use* ; Antispermatogenic Agents ; Cardiovascular Diseases/epidemiology* ; Contraceptive Agents, Male/therapeutic use* ; Gonadotropins/metabolism* ; Humans ; Male ; Progestins/therapeutic use* ; Testosterone/therapeutic use*

Pulsatile gonadotropin-releasing hormone (GnRH) may induce spermatogenesis in most patients with congenital hypogonadotropic hypogonadism (CHH) by stimulating gonadotropin production, while the predictors for a pituitary response to pulsatile GnRH therapy were rarely investigated. Therefore, the aim of our study is to investigate predictors of the pituitary response to pulsatile GnRH therapy. This retrospective cohort study included 82 CHH patients who received subcutaneous pulsatile GnRH therapy for at least 1 month. Patients were categorized into poor or normal luteinizing hormone (LH) response subgroups according to their LH level (LH <2 IU l^-1 or LH ≥2 IU l^-1) 1 month into pulsatile GnRH therapy. Gonadotropin and testosterone levels, testicular size, and sperm count were compared between the two subgroups before and after GnRH therapy. Among all patients, LH increased from 0.4 ± 0.5 IU l^-1 to 7.5 ± 4.4 IU l^-1 and follicle-stimulating hormone (FSH) increased from 1.1 ± 0.9 IU l^-1 to 8.8 ± 5.3 IU l^-1. A Cox regression analysis showed that basal testosterone level (β = 0.252, P = 0.029) and triptorelin-stimulated FSH_60min(β = 0.518, P = 0.01) were two favorable predictors for pituitary response to GnRH therapy. Nine patients (9/82, 11.0%) with low LH response to GnRH therapy were classified into the poor LH response subgroup. After pulsatile GnRH therapy, total serum testosterone level was 39 ± 28 ng dl^-1 versus 248 ± 158 ng dl^-1 (P = 0.001), and testicular size was 4.0 ± 3.1 ml versus 7.9 ± 4.5 ml (P = 0.005) in the poor and normal LH response subgroups, respectively. It is concluded that higher levels of triptorelin-stimulated FSH_60minand basal total serum testosterone are favorable predictors of pituitary LH response to GnRH therapy.
Adult ; Cohort Studies ; Follicle Stimulating Hormone/blood* ; Gonadotropin-Releasing Hormone/therapeutic use* ; Gonadotropins/blood* ; History, 16th Century ; Humans ; Hypogonadism/pathology* ; Luteinizing Hormone/blood* ; Male ; Pituitary Gland/pathology* ; Predictive Value of Tests ; Retrospective Studies ; Sperm Count ; Testis/pathology* ; Testosterone/blood* ; Treatment Outcome ; Triptorelin Pamoate/therapeutic use* ; Young Adult

OBJECTIVETo investigate the effects of hydro-alcoholic extract of Launaea acanthodes, a blood glucose lowering plant in folk medicine of Iran, on the structure of seminiferous tubules and serum gonadotropin and testosterone levels in hyperglycemic rats.

METHODSTwenty-four Wistar rats were randomly allocated into 4 groups (n=6): control, streptozotocin (STZ), STZ + insulin [STZ + Ins, 5 IU/(kg•day)], and STZ + Launaea acanthodes extract [STZ + Ext, 150 mg/(kg•day)]. Blood samples were collected at the 2nd and 4th weeks for detection of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) with enzyme-linked immuno sorbent assay (ELISA), and the right testes of rats were removed at the 7th week for the evaluation of diameter and wall thickness of seminiferous tubules and number of Leydig cells using unbiased stereological techniques.

RESULTSIn comparison with the control group, at the 2nd week FSH (0.45 vs 0.03, 0.02, 0.02 IU/L in STZ, STZ + Ins and STZ + Ext groups, respectively) and LH (1.02 vs 0.37, 0.2, 0.29 IU/L) showed significant decreases (all P<0.05) and testosterone (4.2 vs 8.37, 7.78, 11.8 ng/mL) showed a remarkable increase (all P<0.05). The levels of these hormones became closer in the STZ + Ext and the STZ + Ins groups to the control at the 4th week. A significant decrease in diameter and wall thickness of seminiferous tubules and number of Leydig cells were observed in the STZ group as compared with the control (P<0.01).

CONCLUSIONSAdministration of Launaea extract demonstrated a beneficial impact on the protection of testis from pathogenic and degenerative effects of hyperglycemia which may be partly due to its potential antioxidative effects.

Animals ; Asteraceae ; chemistry ; Blood Glucose ; metabolism ; Cell Count ; Cholesterol ; blood ; Ethanol ; chemistry ; Gonadotropins ; blood ; Hyperglycemia ; blood ; drug therapy ; pathology ; Insulin ; blood ; Leydig Cells ; drug effects ; pathology ; Lipoproteins ; blood ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats, Wistar ; Seminiferous Tubules ; drug effects ; pathology ; Testosterone ; blood ; Triglycerides ; blood ; Water ; chemistry

OBJECTIVETo investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) in women with secondary infertility.

METHODSThe clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone (GnRH) agonist long protocol, GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged ≥ 40 years.

RESULTSAmong 1129 cycles, 376 cases (33.30%) had clinical pregnancy and 753 cases (66.70%) had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups (P<0.05); while only maternal age (OR=0.900, 95% CI: 0.873~0.928, P<0.001) and the number of embryos transferred (OR=2.248, 95% CI: 1.906~2.652, P<0.001) were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged ≥ 40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation (P>0.05).

CONCLUSIONMaternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol, GnRH agonist short protocol or GnRH antagonist protocol.

Adult ; Embryo Transfer ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; agonists ; Gonadotropins ; Hormone Antagonists ; therapeutic use ; Humans ; Infertility, Female ; Maternal Age ; Ovarian Follicle ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

OBJECTIVETo evaluate the ovarian response and pregnancy outcomes in patients with excessive ovarian response receiving long-protocol pituitary down-regulation during repeated in vitro fertilization and embryo transfer (IVF-ET).

METHODSSixty IVF-ET cycles from January 2008 to December 2011 were analyzed retrospectively. The clinical characteristics were compared between the various treatment cycles.

RESULTSCompared with those with the first treatment cycle, the patients receiving repeated cycles had a significantly older age (P<0.001), reduced initial doses of Gn (P=0.049), and moderately lowered estrogen level on the day of hCG administration (E₂) (P=0.027) and the number of oocytes retrieved (P=0.030). The high-quality embryo formation rate (P<0.001) and clinical pregnancy rate (P=0.009) were both significantly higher in patients with repeated cycles. The dose for down-regulation, total Gn dose, duration of Gn stimulation, number of two pronuclei (PN), number of fertilized oocyte, and the cancellation rate for a high risk of ovarian hyperstimulation syndrome (OHSS) were all comparable between the two groups (P>0.05). The recurrence rate of ovarian excessive respond was 40% (12/30).

CONCLUSIONSFor patients receiving repeated IVF treatment cycle with a high ovarian response, a smaller initial dose of Gn should be used to minimize the risk of hyper-response and improve the outcome of assisted reproductive treatment.

Down-Regulation ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropins ; therapeutic use ; Humans ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies ; Risk Factors

We report 3 cases of polycystic ovary syndrome (PCOS) in which the patients had successful pregnancy after repeated implantation failure in at least 8 in vitro fertilization and embryo transfer (IVF-ET) cycles. The patients were treated with gonadotropin-releasing hormone antagonist (GnRH-ant) protocol and gonadotropin-releasing hormone angonist (GnRHa) for triggering ovulation, and successful pregnancy and normal deliveries were achieved after 9 IVT-ET cycles. For young patients with PCOS but a good ovarian reserve and a high ovarian response, treatment with GnRH antagonist protocol and GnRHa alone with appropriate management of the factors that may affect implantation can prevent severe ovarian hyperstimulation syndrome to achieve favorable clinical outcomes.
Embryo Implantation ; Embryo Transfer ; Female ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; agonists ; antagonists & inhibitors ; Gonadotropins ; Hormone Antagonists ; therapeutic use ; Humans ; Ovarian Hyperstimulation Syndrome ; Ovulation ; Ovulation Induction ; Polycystic Ovary Syndrome ; Pregnancy ; Pregnancy Outcome

OBJECTIVETo observe the effect of Yougui Formula Granule (YFG) on ovarian granulosa cells gene expression profiles in in vitro fertilization-embryo transfer (IVF-ET) patients of Shen yang deficiency syndrome (SYDS) from the viewpoint of genomics.

METHODSTotally 72 infertility patients undergoing IVF-ET were randomly assigned to the treatment group and the control group according to random digit table, 36 in each group. Patients in the treatment group took YFG combined gonadotropin (Gn), while those in the control group took placebos combined Gn. All medication lasted for 3 menstrual cycles before IVF. With high-throughput gene sequencing technology, gene expression profiles of ovarian granulosa cells in the two groups were analyzed to explore the difference by gene ontology (GO) enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.

RESULTSOvarian granulosa cell gene expression profiles from the follicular fluid showed, when compared with the control group, 391 differential genes were found in the syndrome-control group, 153 down-regulated and 238 upregulated. Enrichment of differentially expressed cellular location and molecular function of genes involved cell proliferation and apoptosis associated cyclin, protein ubiquitination, construction of microtubules and microfilament, mitochondrial function and energy-related factors, regulatory factors for hormone synthesis. Participated pathways involved energy metabolism pathway and transforming growth factor-β (TGF-β) signaling pathway.

CONCLUSIONSThere existed significant difference in gene expression profiles of ovarian granulosa cells between the treatment group and the control group. Differentially expressed genes involved in biological processes correlates with Shen yang deficiency induced proliferation of germ cells, confused apoptosis, and hindered process during which mitochondria produced energy.

Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Embryo Transfer ; Female ; Fertilization in Vitro ; Follicular Fluid ; Gene Expression ; drug effects ; Gonadotropins ; Granulosa Cells ; Humans ; Syndrome ; Transcriptome ; Yang Deficiency