-
Medicine Aug 2019To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal gonadotropin (HCG/HMG) intramuscular injection have been performed to treat male hypogonadotropic hypogonadism (HH) spermatogenesis.
METHODS
In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and monthly, as were the serum total testosterone level, testicular volume and spermatogenesis rate in monthly follow-up sessions.
RESULTS
In the GnRH group and HCG/HMG group, the testosterone level and testicular volume at the 6-month follow-up session were significantly higher than were those before treatment. There were 62 patients (62/117, 52.99%) in the GnRH group and 26 patients in the HCG/HMG (26/103, 25.24%) group who produced sperm following treatment. The GnRH group (6.2 ± 3.8 months) had a shorter sperm initial time than did the HCG/HMG group (10.9 ± 3.5 months). The testosterone levels in the GnRH and HCG/HMG groups were 9.8 ± 3.3 nmol/L and 14.8 ± 8.8 nmol/L, respectively.
CONCLUSION
The GnRH pulse subcutaneous infusion successfully treated male patients with HH, leading to earlier sperm production than that in the HCG/HMG-treated patients. GnRH pulse subcutaneous infusion is a preferred method.
Topics: Adolescent; Adult; Chorionic Gonadotropin; Drug Administration Routes; Drug Administration Schedule; Drug Combinations; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Infusion Pumps; Luteinizing Hormone; Male; Menotropins; Reproductive Control Agents; Spermatogenesis; Testosterone; Young Adult
PubMed: 31374027
DOI: 10.1097/MD.0000000000016616 -
Medicine May 2019At present, the precise role of human menopausal gonadotropin (HMG) and recombinant luteinizing hormone (rLH) supplementation at an early time of follicular phase on in... (Observational Study)
Observational Study
A cohort study of both human menopausal gonadotropin (HMG) and recombinant luteinizing hormone addition at early follicular stage in in vitro fertilization outcome: A STROBE-compliant study.
At present, the precise role of human menopausal gonadotropin (HMG) and recombinant luteinizing hormone (rLH) supplementation at an early time of follicular phase on in vitro fertilization (IVF)/intra cytoplasmatic sperm injection (ICSI) outcomes remains uncertain.Here infertile women of normal ovarian function undergoing their first cycle of IVF/ICSI were studied and were randomly allocated into 3 groups. Group 1, ovarian stimulation with 150IU recombinant follicle-stimulating hormone (FSH) alone. Group 2, patients received 75IU rFSH and 75IU HMG. Group 3 patients were given 150IU rFSH and 75IU rLH.There were no significant differences in the clinical characteristics, ovarian response, the biochemical, clinical and ongoing pregnancy rates among the 3 groups. No significant differences were found in biochemical, clinical and ongoing pregnancy rates between the patients whose LH levels were lower than 0.75 mIU/ml and those above this threshold in group 1. Furthermore, there were also no significant differences in biochemical, clinical and ongoing pregnancy rates among the 3 group patients whose LH level lower than 0.75 mIU/ml.The results showed that either the addition of HMG or rLH supplementation at an early time of follicular phase produce no significant benefit on IVF outcome in patients with normal ovarian function.
Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Follicular Phase; Humans; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Young Adult
PubMed: 31083194
DOI: 10.1097/MD.0000000000015512 -
The Cochrane Database of Systematic... Jan 2019Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ovulation induction with follicle stimulating hormone (FSH) is a second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate.
OBJECTIVES
To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS), and women who do not ovulate or conceive after clomiphene citrate.
SEARCH METHODS
In January 2018, we searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, the World Health Organisation clinical trials register, Clinicaltrials.gov, LILACs, and PubMed databases, and Google Scholar. We checked references of in all obtained studies. We had no language restrictions.
SELECTION CRITERIA
All randomised controlled trials reporting data on clinical outcomes in women with PCOS who did not ovulate or conceive on clomiphene citrate, and undergoing ovulation induction with urinary-derived gonadotrophins, including urofollitropin (uFSH) in purified FSH (FSH-P) or highly purified FSH (FSH-HP) form, human menopausal gonadotropin (HMG) and highly purified human menopausal gonadotrophin (HP-HMG), or recombinant FSH (rFSH), or continuing clomiphene citrate. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that described co-treatment with clomiphene citrate, metformin, luteinizing hormone, or letrozole.
DATA COLLECTION AND ANALYSIS
Three review authors (NW, EK, and MvW) independently selected studies for inclusion, assessed risk of bias, and extracted study data. Primary outcomes were live birth rate per woman and multiple pregnancy per woman. Secondary outcomes were clinical pregnancy, miscarriage, incidence of ovarian hyperstimulation syndrome (OHSS) per woman, total gonadotrophin dose, and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the risk ratio (RR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria.
MAIN RESULTS
The review included 15 trials with 2387 women. Ten trials compared rFSH with urinary-derived gonadotrophins (three compared rFSH with human menopausal gonadotrophin, and seven compared rFSH with FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P. One trial compared FSH with continued clomiphene citrate.Recombinant FSH (rFSH) versus urinary-derived gonadotrophinsThere may be little or no difference in the birth rate between rFSH and urinary-derived gonadotrophins (RR 1.21, 95% confidence interval (CI) 0.83 to 1.78; five trials, N = 505; I² = 9%; low-quality evidence). This suggests that for the observed average live birth per woman who used urinary-derived FSH of 16%, the chance of live birth with rFSH is between 13% and 28%. There may also be little or no difference between groups in incidence of multiple pregnancy (RR 0.86, 95% CI 0.46 to 1.61; eight trials, N = 1368; I² = 0%; low-quality evidence), clinical pregnancy rate (RR 1.05, 95% CI 0.88 to 1.27; eight trials, N = 1330; I² = 0; low-quality evidence), or miscarriage rate (RR 1.20, 95% CI 0.71 to 2.04; seven trials, N = 970; I² = 0; low-quality evidence). We are uncertain whether rFSH reduces the incidence of OHSS (RR 1.48, 95% CI 0.82 to 2.65, ten trials, n=1565, I² = 0%, very low-quality evidence).Human menopausal gonadotrophin (HMG) or HP-HMG versus uFSHWhen compared to uFSH, we are uncertain whether HMG or HP-HMG improves live birth rate (RR 1.28, 95% CI 0.65 to 2.52; three trials, N = 138; I² = 0%; very low quality evidence), or reduces multiple pregnancy rate (RR 2.13, 95% CI 0.51 to 8.91; four trials, N = 161; I² = 0%; very low quality evidence). We are also uncertain whether HMG or HP-HMG improves clinical pregnancy rate (RR 1.31, 95% CI 0.66 to 2.59; three trials, N = 102; I² = 0; very low quality evidence), reduces miscarriage rate (RR 0.33, 95% CI 0.06 to 1.97; two trials, N = 98; I² = 0%; very low quality evidence), or reduces the incidence of OHSS (RR 7.07, 95% CI 0.42 to 117.81; two trials, N = 53; very low quality evidence) when compared to uFSH.Gonadotrophins versus continued clomiphene citrateGonadotrophins resulted in more live births than continued clomiphene citrate (RR 1.24, 95% CI 1.05 to 1.46; one trial, N = 661; I² = 0%; moderate-quality evidence). This suggests that for a woman with a live birth rate of 41% with continued clomiphene citrate, the live birth rate with FSH was between 43% and 60%. There is probably little or no difference in the incidence of multiple pregnancy between treatments (RR 0.89, 95% CI 0.33 to 2.44; one trial, N = 661; I² = 0%; moderate-quality evidence). Gonadotrophins resulted in more clinical pregnancies than continued clomiphene citrate (RR 1.31, 95% CI 1.13 to 1.52; one trial, N = 661; I² = 0%; moderate-quality evidence), and more miscarriages (RR 2.23, 95% CI 1.11 to 4.47; one trial, N = 661; I² = 0%; moderate-quality evidence). None of the women developed OHSS.
AUTHORS' CONCLUSIONS
There may be little or no difference in live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate between urinary-derived gonadotrophins and recombinant follicle stimulating hormone in women with polycystic ovary syndrome. For human menopausal gonadotropin or highly purified human menopausal gonadotrophin versus urinary follicle stimulating hormone we are uncertain whether one or the other improves or lowers live birth, incidence of multiple pregnancy, clinical pregnancy rate, or miscarriage rate. We are uncertain whether any of the interventions reduce the incidence of ovarian hyperstimulation syndrome. We suggest weighing costs and convenience in the decision to use one or the other gonadotrophin. In women with clomiphene citrate failure, gonadotrophins resulted in more live births than continued clomiphene citrate without increasing multiple pregnancies.
Topics: Abortion, Spontaneous; Birth Rate; Clomiphene; Drug Resistance; Female; Fertility Agents, Female; Follicle Stimulating Hormone; Gonadotropins; Humans; Live Birth; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy, Multiple; Randomized Controlled Trials as Topic
PubMed: 30648738
DOI: 10.1002/14651858.CD010290.pub3 -
JBRA Assisted Reproduction Apr 2019Some of the common side effects of the injectable gonadotropins, used during fertility treatments, are pain at the injection site, skin erythema, muscle pain, and rarely...
Some of the common side effects of the injectable gonadotropins, used during fertility treatments, are pain at the injection site, skin erythema, muscle pain, and rarely vasovagal reflex. These side effects cause inconvenience and lower patient's tolerance for fertility treatments.The purpose of this study was to evaluate the safety and efficacy of an FDA-approved dose of nasal human menopausal gonadotropins (Menopur) in women undergoing fertility treatment. Healthy regularly cycling reproductive-aged women (n=4) with infertility were enrolled. A total of 75 IU of each Menopur bottle was dissolved and placed in a nasal pump spray device (concentration of 3.75 IU/spray). Each participant was allowed to inhale a total of 2 sprays daily after which ovarian response during the follicular phase was monitored by transvaginal ultrasound and serum hormone measurement. None of the participants reported any side effects at the nasal site of drug administration. No known common side effects of the Menopur drug were reported by any of the participants. Despite adequate absorption of the nasal Menopur, as confirmed by elevated serum FSH levels while taking the nasal medication, 3 out of 4 participants did not show any follicular growth until cycle day 13 while only one participant who agreed to continue taking the medication until cycle day 20 developed one dominant follicle and had elevated serum estradiol levels. This FDA approved case series suggest that nasal route of Menopur administration seems to be safe at a very low doses and it constitutes a potential novel approach for ovarian stimulation.
Topics: Administration, Intranasal; Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Humans; Infertility, Female; Menotropins; Nasal Sprays; Ovarian Follicle; Ovulation Induction
PubMed: 30500132
DOI: 10.5935/1518-0557.20180078 -
Sheng Li Xue Bao : [Acta Physiologica... Oct 2018The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian...
The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian hyperstimulation (COH) on embryo implantation in mice. Forty female Kunming mice aged 9 weeks were randomly divided into two groups (control and COH groups). The COH group received intraperitoneal (i.p.) injections of aminocyclin acetate (GnRHa), human menopausal gonadotropin (HMG) and human chorionic gonadotropin (hCG), while the control group was given equal amount of physiological saline by i.p. injection. One male mouse and two female mice were put into the same cage at 16:00 on the hCG injection day, and on the fourth day of pregnancy, 10 mice from each group were killed. The levels of serum estradiol (E) and progesterone (P) were measured by radioimmunoassay; HE staining was used to observe the morphology of ovarian and endometrial tissues. The protein expression levels of endometrial leukemia inhibitory factor (LIF), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and glycodelin A were detected by Western blot and immunohistochemistry. Ten mice from each group were sacrificed on the eighth day of pregnancy, and the status of the uterus and the average number of blastocysts were observed. The results showed that, compared with control group, the serum E level in COH group was significantly decreased (P < 0.05), while the P level was increased significantly (P < 0.05); the ovarian follicles at different developmental stages were rare, corpus lutea (CL) were visible and multiple, the endometrium was thinned, and the number of endometrial glands was reduced (P < 0.05); the contents of LIF, p-STAT3, HB-EGF and glycodelin A in the endometrium were decreased significantly (P < 0.05) on the fourth day of pregnancy; mouse blastocysts developed slowly and were decreased in number on the eighth day of pregnancy (P < 0.05). The above results suggest that GnRHa COH can affect embryo implantation in mice. The mechanism may be related to the imbalance of gonadal hormone, the changes in the structure of the endometrium and the expressions of LIF, p-STAT3, HB-EGF and glycodelin A in the implantation stage, which may lead to the decrease of endometrial receptivity and the abnormal dialogue between the embryo and the uterus.
Topics: Animals; Chorionic Gonadotropin; Embryo Implantation; Endometrium; Estradiol; Female; Glycodelin; Gonadotropin-Releasing Hormone; Humans; Leukemia Inhibitory Factor; Menotropins; Mice; Minocycline; Ovarian Follicle; Ovulation Induction; Pregnancy; Progesterone; Random Allocation; STAT3 Transcription Factor
PubMed: 30377687
DOI: No ID Found -
Reproductive Biology and Endocrinology... Sep 2018Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via...
BACKGROUND
Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear.
METHODS
Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective.
RESULTS
A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution.
CONCLUSIONS
Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02544191 .
Topics: Adult; Azoospermia; Case-Control Studies; Chorionic Gonadotropin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Inhibins; Male; Menotropins; Middle Aged; Pilot Projects; Spermatogenesis; Zonula Occludens-1 Protein
PubMed: 30243299
DOI: 10.1186/s12958-018-0401-7 -
Neonate female to male ratio after assisted reproduction following antagonist and agonist protocols.Medicine Sep 2018We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic... (Observational Study)
Observational Study
We retrospectively compared neonatal sex after antagonist- versus long-stimulation protocols followed by fresh in vitro fertilization (IVF) or fresh intracytoplasmic sperm injection (ICSI) with either protocol. We reviewed data for 762 IVF/ICSI cycles in 2015, including 23 IVF procedures. We summarized sex outcomes in the entire cohort, and for the additional subgroups: embryo transfer day and number of embryos transferred, and number of oocytes recovered and maternal age. Among 169 live births for all protocols combined, 50.9% of babies were male, and we saw no difference between the antagonist versus long-stimulation groups (52.3% vs 48.3% male babies, respectively; P = .740). Our results also showed no significant difference in sex proportion when comparing IVF versus ICSI, although a higher proportion of babies were male with the antagonist-ICSI protocol. Differences between the additional subgroups were also neither clinically nor statistically significant.
Topics: Adult; Chorionic Gonadotropin; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infant, Newborn; Leuprolide; Male; Maternal Age; Menotropins; Oocytes; Retrospective Studies; Saudi Arabia; Sex Ratio; Socioeconomic Factors; Sperm Injections, Intracytoplasmic
PubMed: 30235681
DOI: 10.1097/MD.0000000000012310 -
Scientific Reports Sep 2018The potential effects of high basal luteinizing hormone (LH) levels on human reproduction were controversial. To demonstrate the effects of elevated basal LH levels on...
The potential effects of high basal luteinizing hormone (LH) levels on human reproduction were controversial. To demonstrate the effects of elevated basal LH levels on the outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles, we performed a retrospective data analysis of 1011 polycystic ovarian syndrome (PCOS) patients treated with human menopausal gonadotropin and medroxyprogesterone acetate (hMG + MPA) protocol at our center between Nov. 2013 and Jun. 2017. PCOS patients with elevated basal LH levels had significantly higher LH exposure during the stimulation period. The group with LH ≥ 10 mIU/mL showed a lower mean total hMG dose used but higher numbers of oocytes retrieved, metaphase II oocytes, embryos and top-quality embryos developed than the groups with lower basal LH levels. Moreover, partial correlation analysis showed that the basal LH level was negatively correlated with the total hMG dose but positively correlated with the numbers of oocytes retrieved, metaphase II oocytes, embryos, and top-quality embryos. There were no significant differences in the rates of oocyte retrieval, fertilization, implantation, clinical pregnancy and miscarriage between the groups based on frozen embryo transfer (FET). We concluded that elevated basal LH level does not impair the final outcome of hMG + MPA-treated IVF/ICSI cycles in PCOS women.
Topics: Adult; Embryo Implantation; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropins; Humans; Infertility, Female; Luteinizing Hormone; Medroxyprogesterone Acetate; Menotropins; Middle Aged; Oocyte Retrieval; Oocytes; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Retrospective Studies; Sperm Injections, Intracytoplasmic
PubMed: 30217999
DOI: 10.1038/s41598-018-32128-4 -
American Journal of Obstetrics and... Sep 2018
Topics: Endocrinology; Fertility Agents, Female; History, 20th Century; History, 21st Century; Infertility; Menotropins; Reproductive Medicine
PubMed: 30170793
DOI: 10.1016/j.ajog.2018.06.019 -
Trials Aug 2018Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve... (Comparative Study)
Comparative Study Randomized Controlled Trial
Gonadotropin-releasing hormone antagonist versus progestin for the prevention of premature luteinising hormone surges in poor responders undergoing in vitro fertilisation treatment: study protocol for a randomised controlled trial.
BACKGROUND
Progress in vitrification techniques has allowed reproductive physicians to consider new strategies for using progestin as an alternative to a GnRH analogue to improve in vitro fertilisation (IVF). However, the role of progestin in blocking luteinising hormone (LH) surges and its potential in clinical practice are unclear, especially for poor responders. We designed a prospective randomised controlled trial (RCT) to compare the efficacy of a gonadotropin-releasing hormone (GnRH) antagonist and progestin in blocking LH surges and premature ovulation in poor responders.
METHODS/DESIGN
Poor responders who meet the Bologna criteria will be randomised to one of two stimulation regimens-gonadotropin-releasing hormone (GnRH) antagonist or progestin-primed ovarian stimulation (PPOS)-using a computer-generated random number. Fresh embryos were transferred in the GnRH antagonist group and frozen embryos were transferred in the PPOS group. The primary outcome is the incidence of premature LH surges. Secondary outcomes include the number of oocytes retrieved, the number of embryos available for transfer, implantation rates and clinical pregnancy. The sample size for this trial is estimated as 340 participants, with 170 participants in each group. The data analysis will be by intention to treat.
DISCUSSION
To our knowledge, this is the first RCT to examine the efficacy of administering progestin orally to block LH surges and premature ovulation compared with the GnRH antagonist protocols in poor responders undergoing IVF treatment.
TRIAL REGISTRATION
www.chictr.org.cn . ChiCTR-IPR-17010906 . Registered on 18 March 2017.
Topics: Administration, Oral; Adult; Biomarkers; China; Clinical Protocols; Cryopreservation; Embryo Implantation; Embryo Transfer; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Male; Medroxyprogesterone Acetate; Menotropins; Oocyte Retrieval; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone Congeners; Prospective Studies; Research Design; Sperm Injections, Intracytoplasmic; Treatment Outcome; Young Adult
PubMed: 30134964
DOI: 10.1186/s13063-018-2850-x