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.
Adolescent ; Adult ; Child ; Chorionic Gonadotropin/therapeutic use* ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism/drug therapy* ; Male ; Menotropins/therapeutic use* ; Spermatogenesis ; Testosterone

Gonadotropin therapy is commonly used to induce virilization and spermatogenesis in male isolated hypogonadotropic hypogonadism (IHH) patients. In clinical practice, 5.6%-15.0% of male IHH patients show poor responses to gonadotropin treatment; therefore, testosterone (T) supplementation can serve as an alternative therapy to normalize 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 undecanoate (TU) supplementation 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) months 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.
Adolescent ; Adult ; Chorionic Gonadotropin/therapeutic use* ; Drug Therapy, Combination ; Follicle Stimulating Hormone/blood* ; Humans ; Hypogonadism/drug therapy* ; Luteinizing Hormone/blood* ; Male ; Retrospective Studies ; Spermatogenesis/drug effects* ; Testosterone/therapeutic use* ; Treatment Outcome ; Young Adult

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

Objective: To investigate whether the trigger effect of human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG) attributes to the treatment of unexplainable non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data about 282 cases of unexplainable NOA treated in the Maternity and Child Health Hospital of Guizhou Province from January 2010 to May 2017. All the patients underwent trigger treatment by intramuscular injection of hMG at 75 IU 3 times a week for 2 weeks, followed by hCG at 2 000 IU twice a week for another 2 weeks, and meanwhile took vitamin E, Levocarnitine and Tamoxifen as an adjunctive therapy. The treatment lasted 3－12 months. RESULTS: Fifty-eight of the 255 patients that completed the treatment were found with sperm in the semen after treatment, all with severe oligoasthenospermia. Forty-seven of the 58 cases received assisted reproductive technology (ART), of which 18 achieved clinical pregnancy. Semen centrifugation revealed no sperm in the other cases, of which 6 were found with epididymal sperm at epididymal and testicular biopsy after treatment and 3 of them achieved clinical pregnancy after ART. Sperm was found in the semen or at epididymal or testicular biopsy in 64 of the patients after treatment, with an effectiveness rate of 25.1%. CONCLUSIONS Trigger treatment by injection of hMG and hCG combined with adjunctive oral medication has a certain effect on unexplainable NOA.
Azoospermia ; drug therapy ; Chorionic Gonadotropin ; therapeutic use ; Drug Administration Schedule ; Epididymis ; Female ; Fertility Agents, Male ; therapeutic use ; Humans ; Injections, Intramuscular ; Male ; Menotropins ; therapeutic use ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Retrospective Studies ; Sperm Retrieval ; statistics & numerical data ; Spermatozoa ; Testis

ObjectiveTo analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment.

METHODSWe retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15).

RESULTSThe average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either.

CONCLUSIONSHypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

Adult ; Chorionic Gonadotropin ; therapeutic use ; Follicle Stimulating Hormone ; blood ; Humans ; Hypogonadism ; diagnosis ; etiology ; therapy ; Luteinizing Hormone ; blood ; Male ; Pituitary Neoplasms ; blood ; complications ; pathology ; therapy ; Prolactinoma ; blood ; complications ; pathology ; therapy ; Retrospective Studies ; Sella Turcica ; Spermatogenesis ; Spermatozoa ; Testis ; anatomy & histology ; drug effects ; Testosterone ; analogs & derivatives ; blood ; therapeutic use ; Tumor Burden

OBJECTIVETo study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET).

METHODSTotally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups.

RESULTSThe total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05).

CONCLUSIONSGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos.

Adjuvants, Pharmaceutic ; therapeutic use ; Chorionic Gonadotropin ; Drugs, Chinese Herbal ; therapeutic use ; Embryo Transfer ; methods ; Estradiol ; Female ; Fertilization in Vitro ; methods ; Follicle Stimulating Hormone ; metabolism ; therapeutic use ; Follicular Fluid ; Humans ; Medicine, Chinese Traditional ; Oocyte Retrieval ; Oocytes ; Ovarian Hyperstimulation Syndrome ; Ovulation Induction ; Pregnancy ; Pregnancy Rate

INTRODUCTIONIntrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) was applied to selected infertile patients to determine the effect of gonadotropin-releasing hormone (GnRH) antagonists in IUI cycles, in which recombinant follicle-stimulating hormone (rFSH) had been used for COH.

METHODSThis study was conducted between April 1, 2009 and June 10, 2009, and involved a total of 108 patients. These patients had primary or secondary infertility, which resulted in an indication for IUI, and they each received two cycles of ovarian stimulation treatment with clomiphene citrate. The patients were randomised into two groups--patients in group A received rFSH + GnRH antagonist (n = 45), while those in group B received only rFSH (n = 63).

RESULTSThe mean age of the patients was 31.84 ± 3.73 years and the mean body mass index (BMI) was 24.40 ± 1.88 kg/m(2). The mean age and BMI of the patients in groups A and B were not significantly different. There was no significant difference in the mean total rFSH dose administered (988.33 IU in group A and 871.83 IU in group B). When compared to group B, the mean number of follicles that were > 16 mm on the human chorionic gonadotropin (HCG) trigger day was significantly higher in group A (1.58 and 1.86, respectively; p < 0.05). When the two groups were compared, there were no statistically significant differences in the number of cancelled cycles due to premature luteinisation (none in group A vs. two in group B) and the rate of clinical pregnancy (8.9% in group A vs. 7.9% in group B).

CONCLUSIONNo significant improvement in the clinical pregnancy rates was observed when GnRH antagonists were used in COH + IUI cycles, despite the significant increase in the number of follicles that were > 16 mm on HCG trigger day.

Adult ; Body Mass Index ; Chorionic Gonadotropin ; blood ; Clomiphene ; therapeutic use ; Endometrium ; pathology ; Female ; Follicle Stimulating Hormone ; therapeutic use ; Gonadotropin-Releasing Hormone ; antagonists & inhibitors ; Hormone Antagonists ; therapeutic use ; Humans ; Infertility, Female ; therapy ; Insemination, Artificial ; methods ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Rate ; Young Adult

Primary colorectal choriocarcinoma is a rare neoplasm. Only 19 cases have been reported worldwide, most of which involved adenocarcinomas. The prognosis is usually poor, and the standard therapy for this tumor has not been established. A 61-year-old woman presented with constipation and lower abdominal discomfort. She was diagnosed with primary adenocarcinoma with focal choriocarcinomatous differentiation in the sigmoid colon and liver metastasis. Because the serum beta-human chorionic gonadotropin level was not significantly elevated, and because only focal choriocarcinomatous differentiation was diagnosed, we selected the chemotherapy regimen that is used for the treatment of metastatic colorectal adenocarcinoma. The patient survived for 13 months after the initial diagnosis. This is the first case in Korea to assess the suppressive effects of the standard chemotherapy for colorectal adenocarcinoma against coexisting colorectal choriocarcinoma and adenocarcinoma.
Adenocarcinoma/*diagnosis/drug therapy/pathology ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CA-19-9 Antigen/analysis ; Chorionic Gonadotropin, beta Subunit, Human/blood ; Colon, Sigmoid/pathology ; Colonic Neoplasms/*diagnosis/drug therapy/pathology ; Colonoscopy ; Constipation/etiology ; Female ; Fluorouracil/therapeutic use ; Humans ; Leucovorin/therapeutic use ; Liver Neoplasms/secondary ; Middle Aged ; Organoplatinum Compounds/therapeutic use ; Prognosis ; Tomography, X-Ray Computed

OBJECTIVETo study the effect and potential mechanism of Modified Cangfu Daotan Decoction (MCDD) on endometrial receptivity in infertility patients with polycystic ovarian syndrome (PCOS).

METHODSTotally 298 women having normal ovulation who underwent artificial insemination were recruited as the control group, and they received no drug therapy. Another 355 infertility patients with PCOS who received ovarian stimulation therapy were recruited as the treatment group. Then they were further assigned to the treatment group I (195 cases) and the treatment group II (160 cases) according to random digit table. Patients in the treatment group I received clomiphene (CC) + human menopause gonadotropin (HMG) +human chorionic gonadotropin (HCG), while those in the treatment group II received CC + HMG + HCG and additionally took modified MCDD. The therapeutic course for all was three menstrual cycles. The pregnancy ratio, the endometrial thickness, and spiral artery pulsatility index (PI), resistance index (RI), and homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Furthermore, the uncoupling protein 2 (UCP2) level was tested by Western blot.

RESULTSCompared with the control group, the endometrial thickness decreased and PI and RI increased in the treatment group I (all P < 0.05). Compared with the treatment group I , the endometrial thickness increased and PI and RI decreased in the treatment group II (all P < 0.05). Compared with before treatment, HOMA-IR levels were significantly decreased in the treatment group II after treatment (P < 0.05). Compared with the control group before treatment, the HOMA-IR level increased in the treatment group I and the treatment group II before treatment (P < 0.05). Compared with the control group after treatment, the HOMA-IR level increased in the treatment group I (P < 0.05). But there was no statistical difference in the post-treatment HOMA-IR level between the control group and the treatment group II (P < 0.05). Compared with the control group, the post-treatment UCP2 level was increased in the treatment group II (P < 0.05). After one year follow-up, the pregnancy rate was 16.1% (48/298) in the control group, 23.1% (37/160) in the treatment group I, and 33.8% (66/195) in the treatment group II. Compared with the control group, the pregnancy rate was significantly increased in the treatment group II (P < 0.05).

CONCLUSIONMCDD was found to be capable of increasing the pregnancy rate of infertility patients with PCOS, which might be associated with improving endometrial blood flow and insulin resistance, increasing the UCP2 expression, and finally improving the endometrial receptivity.

Chorionic Gonadotropin ; Clomiphene ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gonadotropins ; Humans ; Infertility ; Infertility, Female ; Insulin Resistance ; Ovulation ; Ovulation Induction ; methods ; Polycystic Ovary Syndrome ; drug therapy ; Pregnancy ; Pregnancy Rate

BACKGROUNDThe successful end-point of in vitro fertilization (IVF) treatment is for a woman to give live birth. This outcome is based on various factors including adequate number of retrieved eggs. Failure to recruit adequate follicles, from which the eggs are retrieved, is called a "poor response". How to improve the clinical pregnancy rates of poor responders was one of the tough problems for IVF.

METHODSThe study involved 51 patients who responded poorly to high dose gonadotropin treatment in their previous cycles at our reproductive center, between April 2010 and February 2012. The previous cycle (group A) received routine long protocol; the subsequent cycle (group B) received modified super-long down-regulation protocol. The primary outcome of the study was the number of oocytes fertilized. The increase in the pregnancy rate was the secondary outcome. Differences between the groups were assessed by using Student's t test and c(2) test where appropriate.

RESULTSThe patients' average age was (36.64 ± 3.85) years. The mean duration of ovarian stimulation cycles of the group A patients was longer than those of the group B patients. The total dose of follicle-stimulating hormone (FSH) was significantly lower in the subsequent cycle. The peak value of serum estradiol on human chorionic gonadotrophin (hCG) day was lower in group A as compared with group B. The number of metaphase II oocytes recovered was significantly higher in group B. The cleavage rate in group A was significantly lower than in group B, 49 patients in group B reached embryo transfer stage, while 46 patients in group A reached this stage. Patients in group B received significantly more embryos per transfer as compared with group A. More pregnancies and more clinical pregnancies with fetal heart activity were achieved in group B.

CONCLUSIONSThis comparative trial shows that poor responder women undergoing repeated assisted reproduction treatment using modified super-long down-regulation protocol achieve more oocytes, leading to higher fertilization rate, compared to women receiving routine long protocol. Our study also showed that clinical pregnancy rate was significantly improved.

Adult ; Chorionic Gonadotropin ; therapeutic use ; Embryo Transfer ; Estradiol ; blood ; Female ; Fertilization in Vitro ; methods ; Follicle Stimulating Hormone ; therapeutic use ; Humans ; Male ; Ovulation Induction ; methods ; Pregnancy