Urinary FSH Research Articles

The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells.

Different Follicle Stimulating Hormone (FSH) formulation and Luteinizing Hormone (LH) are used in Assisted Reproductive Technology (ART) to induce follicles development and oocytes maturation, but it is still under debate which protocol is to be preferred. In the present study, the different effects on cumulus cells (CCs) of three controlled ovarian stimulation (COS) protocols, based on urinary FSH, recombinant FSH, or human Menopausal Gonadotropin (hMG) administration, were assessed. CCs were obtained from 42 normal-responders women undergoing COS, randomly divided into three groups according to the used gonadotropin formulation. Differences were found in the expression of genes belonging to the endocannabinoid system (the receptors CNR1, CNR2 and TRPV1, and the enzymes involved in the metabolisms of anandamide, NAPE-PLD and FAAH, and 2-acylglycerol, DAGL and MAGL); consistently, changes in lipid (PPARα, and FASN) and carbohydrate (GLUT1 and GLUT9) metabolisms, in CCs’ macromolecules composition (highlighted by Fourier Transform Infrared Microspectroscopy, FTIRM), and in the number of retrieved oocytes were found. For the first time, statistically significant evidence on the differences related to each COS protocol on the endocannabinoid system, metabolism and macromolecular composition of CCs was found, representing a proof of concept to be further confirmed in a larger cohort of patients.

Correlation between Urinary Bisphenol A (BPA) Levels and Male Reproductive Functions among Sample of Egyptian Population

BPA as a xenoestrogen negatively influences male reproductive functions as well as sperm quality. This study aimed at evaluating the correlation between urinary BPA concentrations and male fertility by assessing semen parameters as well as hormone profile. It included (150) males divided into two groups; infertile cases (n= 100) and fertile controls (n= 50). Results showed highly significant difference in mean urinary BPA concentrations between both groups being higher among infertile group (P-value < 0.001). Besides that, there was statistically significant correlation between the mean urinary BPA concentrations and deterioration of sperm concentration and motility among cases with P-values (< 0.001). Finally, there was statistically significant correlation between mean urinary BPA and hormone levels FSH, LH, T and E2 levels with P-values 0.002, 0.033, 0.001 and < 0.001 respectively.

Phthalate exposure and semen quality in infertile male population from Tianjin, China: Associations and potential mediation by reproductive hormones

Global decline in male fertility and their associations with ubiquitous exposure of phthalates (PAEs) have raised public concerns. However, the current epidemiological data are limited and controversial. Hence, we investigated possible associations between PAE exposure and male infertility. Eleven phthalate metabolites (mPAEs) were determined in urine and serum samples collected from eighty-eight males diagnosed with infertility from Tianjin, China. The median serum levels of mPAE were n.d. −3.63 ng/mL, which were 1–2 orders of magnitude lower than the urinary levels of n.d. −192 ng/mL. Negative associations were identified between urinary follicle-stimulating hormone (FSH) and MiBP and serum MCMHP, as well as testosterone (T) and luteinizing hormone (LH) and the molar concentrations of ∑mPAE, while positive association was found between T and the serum molar concentrations of ∑mDEHP. Positive associations were found between the molar concentrations of serum ∑mPAE and sperm concentration, sperm motility rate, and progressive motility, between mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) and semen volume and total sperm number, and between MCMHP and progressive motility, while negative association was found between mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and progressive motility. Moreover, FSH was found to mediate the association between serum concentrations of MCMHP and progressive motility (mediation ratio = 41.6%), and LH to mediate the associations between serum concentrations of ∑mPAE and sperm concentration (mediation ratio = 45.7%) and sperm motility rate (mediation ratio = 29.0%). These results also suggested that serum levels of mPAE are a good predictor for male infertility. Further efforts need to be made on toxicological studies to systematically elaborate the internal mechanisms.

Gonadotropin Treatment for the Male Hypogonadotropic Hypogonadism.

Hypogonadotropic hypogonadism (HH) is caused by a dysfunction in the hypothalamus and/or the pituitary gland and it can be congenital or acquired. This condition is biochemically characterized by low or inappropriately normal gonadotropin levels along with low total testosterone levels. If fertility is not an issue, testosterone therapy is the treatment of choice to induce and maintain secondary sexual characteristics and sexual function. Spermatogenesis is frequently impaired in patients with HH, but usually responsive to hormonal therapy such as gonadotropin therapy or GnRH supplementary/replacement therapy. When gonadotropins are the choice of treatment, conventional therapy includes human chorionic gonadotropin (hCG) along with different FSH formulations: human menopausal gonadotropins (hMG), highly purified urinary FSH preparations (hpFSH) (e.g., urofollitropin) or recombinant FSH (rFSH). The combination of FSH and hCG demonstrated to be associated with better outcomes than single compounds, whereas similar results were obtained with different FSH preparations in male individuals; both regarding the ability to stimulate spermatogenesis and eventually inducing physiology pregnancy. Gonadotropins can be administered either subcutaneously or intramuscularly. The combination therapy with hCG and FSH for a period of 12-24 months was found to promote testicular growth in almost all patients, spermatogenesis in approximately 80% and pregnancy rates in the range of 50%. Gynecomastia is the most common side effect of gonadotropin therapy and is due to hCG stimulation of aromatase causing increased secretion of estradiol. The therapeutic success is higher in patients with post-pubertal HH, in those without previously undescended testes, in patients with higher baseline testicular volume, who underwent repeated cycles of therapy and in patients with higher baseline inhibin B serum concentrations. Reversal of hypogonadism can occur in up to 10% of patients but its physiopathologic mechanism has yet to be elucidated. In conclusion, gonadotropin therapy is effective in promoting puberty and in supporting spermatogenesis onset and preservation in HH patients with either hypothalamic or pituitary conditions.

Does an FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? A randomized, double-blinded, placebo-controlled study.

Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000-10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI -6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). 20 May 2012. 10 June 2012.

Endometrial thickness as a biomarker for ongoing pregnancy in IUI for unexplained subfertility: a secondary analysis.

STUDY QUESTIONWhat is, in couples with unexplained subfertility undergoing IUI, the impact of gonadotrophins compared to clomiphene citrate (CC) on endometrial thickness (EMT) in relation to ongoing pregnancy?SUMMARY ANSWERIn women with unexplained subfertility undergoing IUI with ovarian stimulation, gonadotrophins lead to a thicker endometrium compared to CC, but this does not affect ongoing pregnancy rates.WHAT IS KNOWN ALREADYA systematic review and meta-analysis among couples with unexplained subfertility undergoing IUI with ovarian stimulation showed that women who conceived had, on average, a thicker endometrium than women who did not conceive, but this evidence is not robust due to a high level of heterogeneity. There was insufficient data to draw any conclusions on EMT and the effect on pregnancy outcomes.STUDY DESIGN, SIZE, DURATIONWe performed a secondary analysis of a multicentre randomized controlled superiority trial in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria. In total, 738 couples recruited between July 2013 and March 2016 were allocated to ovarian stimulation with gonadotrophins (n = 369) or with CC (n = 369) for a maximum of four IUI cycles. According to local protocol, recombinant FSH, urinary FSH or hMG was used. Natural conceptions and cancelled cycles were removed from this secondary analysis, as they do not provide any information on pregnancy in relation to stimulation after IUI. Ongoing pregnancy was defined as a positive heartbeat at or beyond 12 weeks of gestation.PARTICIPANTS/MATERIALS, SETTING, METHODSWe first determined the difference in EMT between women randomized to gonadotrophins (75 IU) and CC (100 mg) over all cycles using a linear mixed model. We then investigated the association between EMT and ongoing pregnancy after IUI using a logistic regression model, adjusted for the allocated drug, number of dominant follicles, female age, BMI, duration of subfertility, primary or secondary subfertility, referral status, smoking status, cycle number and total motile sperm count. To conclude, we investigated the association between EMT and ongoing pregnancy by logistic regression separately in women allocated to gonadotrophins and in women allocated to CC.MAIN RESULTS AND THE ROLE OF CHANCEA total of 666 couples underwent 1968 IUI cycles. Of these, 330 couples were allocated to gonadotrophins, of which 85 conceived leading to ongoing pregnancy (rate per cycle 8.9%) and 336 couples were allocated to CC, of which 71 conceived leading to ongoing pregnancy (rate per cycle 7.0%) (relative risk (RR) 1.22, 95% CI 0.92 to 1.61). The mean EMT was 8.9 mm (SD 2.1) in women treated with gonadotrophins and 7.5 mm (SD 2.1) in women treated with CC (adjusted mean difference 1.4 mm; 95% CI: 1.1–1.7). The overall mean EMT was 8.4 mm (SD 2.2) in women that conceived leading to ongoing pregnancy and 8.2 mm (SD 2.2) in women that did not conceive (adjusted odds ratio (OR): 1.03 per 1 mm increase, 95% CI 0.95–1.12). There was no association between EMT and ongoing pregnancy in women treated with gonadotrophins or CC (OR: 1.01 per 1 mm increase, 95% CI 0.90–1.13, and 1.10 per 1 mm increase, 95% CI 0.99–1.23, respectively).LIMITATIONS, REASON FOR CAUTIONSince this is a secondary analysis, the data should be interpreted prudently as secondary analyses are prone to false-positive findings or could be underpowered to show associations that the study is not primarily set up for.WIDER IMPLICATIONS OF THE FINDINGSIn women with unexplained subfertility and treated with IUI, gonadotrophins lead to a significantly thicker endometrium compared to CC, but there was no evidence of a consistent association between EMT in women treated with gonadotrophins or CC and the ongoing pregnancy rate. A relatively thin endometrium after CC is therefore not a valid reason to prefer gonadotrophins as the stimulation agent in IUI for unexplained subfertility.STUDY FUNDING/COMPETING INTEREST(S)The initial trial was funded by the Netherlands Organization for Health Research and Development (ZonMw) (Health Care Efficiency Research; project number: 80-83600-98-10 192). The EudraCT number for this trial was 2013-001034-18. Prof. Dr B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for Merck, ObsEva and Guerbet. The other authors declare no conflicts of interest.TRIAL REGISTRATION NUMBERNTR 4057

Characterization of purified urinary human Follicle stimulating hormone

Characterization of purified urinary human Follicle stimulating hormone

PIH20 A TARGETED LITERATURE REVIEW OF THE ECONOMIC BURDEN ASSOCIATED WITH POLYCYSTIC OVARY SYNDROME

To collate published economic evidence on the cost and resource utilisation associated with polycystic ovary syndrome (PCOS). A literature search was conducted in Embase® and MEDLINE® to identify evidence published from 2009 to 2019. Conference proceedings and bibliographies were also searched. Retrieved studies were included if they were published in English and reported economic burden associated with PCOS. Of the 1079 publications retrieved, six studies were included. One Australian study reported fertility hormone treatment in 33% of PCOS women (Joham et al., 2015). The other – a population-based retrospective cohort study in Australia– reported higher hospitalisation rates for treating gynaecological conditions in PCOS women than in non-PCOS women. Most PCOS women had one hospital admission (77.7%); 12.8% had two admissions and 9.5% had at least three (Hart et al., 2015). In Hungary, the annual health insurance cost of PCOS was HUF78.9 million (€281,160) in 2009 (Boncz et al., 2013). The annual healthcare burden of PCOS associated with type 2 diabetes was at least £237 million in a UK based Bayesian modelling study (Ding et al., 2018). In a randomised study conducted in the Netherlands, the mean cost per first live birth for PCOS women was significantly lower when electrocautery was used to treat clomiphene-resistant PCOS women (€11,176; 95% confidence interval [CI]: €9,689–€12,549) than when recombinant follicle-stimulating hormone was used (€14,423; 95% CI: €12,239–€16,606) (Nahuis et al., 2012). An exogenous low-dose highly purified urinary follicle-stimulating hormone (HP uFSH) step-up protocol with co-administration of clomiphene was cost effective than a low dose step-up HP uFSH protocol in clomiphene-resistant PCOS women (cost-effective ratio: 523 versus 5,236) (Al Boghdady et al., 2012). PCOS is associated with a high economic burden globally. The major contributing factors are infertility, use of fertility hormone treatment, and hospitalisation.

Reduction in FSH Throughout the Menstrual Cycle After Omega-3 Fatty Acid Supplementation in Young Normal Weight but not Obese Women

Dietary fish oil restores ovarian function in subfertile rats, which is thought to be associated with decreased transcription of follicle-stimulating hormone (FSH) β-subunit. We have previously demonstrated a reduction in early follicular serum FSH levels in normal weight but not obese women after treatment with omega-3 polyunsaturated fatty acids (PUFA). Herein, we report the effect of supplementation with omega-3 PUFA on urinary reproductive hormones across the whole menstrual cycle. This interventional study included 17 eumenorrheic women, aged 24–41 years. One month of daily morning urine was collected before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Measurements included urinary FSH, luteinizing hormone (LH) and estrogen and progesterone metabolites, plasma fatty acid composition, and markers of endoplasmic reticulum stress. Compliance with dietary supplementation was verified by significantly reduced ratios of omega-6 to omega-3 PUFA for all subjects after treatment (P <.01). After 1 month of omega-3 PUFA supplementation, urinary FSH was significantly decreased in normal weight, but not obese women, in both follicular and luteal phases (-28.4% and -12.6%, respectively, both P=.04). No significant changes were seen in LH or sex steroids for either weight group. The selective and specific decrease in FSH suggests that omega-3 PUFA supplementation merits further investigation in normal weight women with decreased fertility and/or diminished ovarian reserve.

The Development of Gonadotropins for Clinical Use in the Treatment of Infertility.

The first commercially available gonadotropin product was a human chorionic gonadotropin (hCG) extract, followed by animal pituitary gonadotropin extracts. These extracts were effective, leading to the introduction of the two-step protocol, which involved ovarian stimulation using animal gonadotropins followed by ovulation triggering using hCG. However, ovarian response to animal gonadotropins was maintained for only a short period of time due to immune recognition. This prompted the development of human pituitary gonadotropins; however, supply problems, the risk for Creutzfeld–Jakob disease, and the advent of recombinant technology eventually led to the withdrawal of human pituitary gonadotropin from the market. Urinary human menopausal gonadotropin (hMG) preparations were also produced, with subsequent improvements in purification techniques enabling development of products with standardized proportions of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activity. In 1962 the first reported pregnancy following ovulation stimulation with hMG and ovulation induction with hCG was described, and this product was later established as part of the standard protocol for ART. Improvements in immunopurification techniques enabled the removal of LH from hMG preparations; however, unidentified urinary protein contaminants remained a problem. Subsequently, monoclonal FSH antibodies were used to produce a highly purified FSH preparation containing <0.1 IU of LH activity and <5% unidentified urinary proteins, enabling the formulation of smaller injection volumes that could be administered subcutaneously rather than intramuscularly. Ongoing issues with gonadotropins derived from urine donations, including batch-to-batch variability and a finite donor supply, were overcome by the development of recombinant gonadotropin products. The first recombinant human FSH molecules received marketing approvals in 1995 (follitropin alfa) and 1996 (follitropin beta). These had superior purity and a more homogenous glycosylation pattern compared with urinary or pituitary FSH. Subsequently recombinant versions of LH and hCG have been developed, and biosimilar versions of follitropin alfa have received marketing authorization. More recent developments include a recombinant FSH produced using a human cell line, and a long-acting FSH preparation. These state of the art products are administered subcutaneously via pen injection devices.

Clinical Use of FSH in Male Infertility.

The established clinical indication for FSH use in male infertility is the treatment of patients with hypogonadotropic hypogonadism for stimulation of spermatogenesis that allows the induction of a clinical pregnancy in the female partner and finally the birth of a healthy child. Several clinical studies with urinary, purified, and recombinant FSH preparations in combination with hCG have demonstrated the high treatment efficacy regarding these clinical endpoints. Shortcomings of this hormone therapy are the long duration of treatment, sometimes longer than 2 years, and the inconvenience of injections every second or third day. However, improvements of therapy might be expected with new hormonal treatment options already available for infertility treatment in the female. FSH use for treatment of patients with normogonadotropic idiopathic infertility and oligozoospermia is still considered experimental in most countries. Recent meta-analyses have shown that FSH can significantly increase pregnancy rates in the female partners of these patients, but the effect-size is relatively low. Therefore, predictive factors for treatment success have to be identified, including FSH pharmacogenetics, to select the right normogonadotropic patients with idiopathic infertility for FSH therapy.

An Observational Retrospective Cohort Trial on 4,828 IVF Cycles Evaluating Different Low Prognosis Patients Following the POSEIDON Criteria.

Objective: To study the actual controlled ovarian stimulation (COS) management in women with suboptimal response, comparing clinical outcomes to the gonadotropins consume, considering potential role of luteinizing hormone (LH) addition to follicle-stimulating hormone (FSH).Design: Monocentric, observational, retrospective, real-world, clinical trial on fresh intra-cytoplasmic sperm injection (ICSI) cycles retrieving from 1 to 9 oocytes, performed at Humanitas Fertility Center from January 1st, 2012 to December 31st, 2015.Methods: COS protocols provided gonadotropin releasing-hormone (GnRH) agonist long, flare-up, short and antagonist. Both recombinant and urinary FSH were used for COS and LH was added according to the clinical practice. ICSI outcomes considered were: gonadotropins dosages; total, mature, injected and frozen oocytes; cumulative, transferred and frozen embryos; implantation rate; pregnancy, delivery and miscarriage rates. Outcomes were compared according to the gonadotropin regimen used during COS.Results: Our cohort showed 20.8% of low responders, defined as 1–3 oocytes retrieved and 79.2% of “suboptimal” responders, defined as 4–9 oocytes retrieved. According to recent POSEIDON stratification, cycles were divided in group 1 (6.9%), 2 (19.8%), 3 (11.7%), and 4 (61.5%). The cohort was divided in 3 groups, according to the gonadotropin's regimen. Women treated with FSH plus LH showed worst prognostic factors, in terms of age, basal FSH, AMH, and AFC. This difference was evident in suboptimal responders, whereas only AMH and AFC were different among treatment groups in low responders. Although a different result, in terms of oocytes and embryos detected, major ICSI outcomes (i.e., pregnancy and delivery rates) were similar among groups of COS treatment. Outcomes were significantly different among Poseidon groups. Implantation, pregnancy and delivery rates were significantly higher in Poseidon group 1 and progressively declined in other POSEIDON groups, reaching the worst percentage in group 4.Conclusions: In clinical practice, women with worst prognosis factors are generally treated with a combination of LH and FSH. Despite low prognosis women showed a reduced number of oocytes retrieved, the final ICSI outcome, in terms of pregnancy, is similarly among treatment group. This result suggests that the LH addition to FSH during COS could improve the quality of oocytes retrieved, balancing those differences that are evident at baseline.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03290911

Comparison of recombinant and urinary follicle-stimulating hormones over 2000 gonadotropin-releasing hormone antagonist cycles: a retrospective study

The objective of this paper was to compare the effect of recombinant follicle-stimulating hormone (rFSH) and urinary follicle-stimulating hormone (uFSH) on pregnancy rates and live birth rates with the gonadotropin-releasing hormone (GnRH) antagonist protocol in China. This retrospective study was conducted from January 2014 through August 2017. Patients treated with uFSH had significantly higher levels of luteinizing hormone (3.79 mIU/ml vs. 3.09 mIU/ml) and progesterone (0.93 ng/ml vs. 1.16 ng/ml) on the day of human chorionic gonadotropin (HCG) administration, and they also had higher pregnancy rates (24.19% vs. 22.86%). There was no significant difference in the rate of live births. In the logistic regression results of the rFSH group, the pregnancy rate was positively correlated with the level of luteinizing hormone, with an odds ratio (OR) of 1.09 (95% confidence interval [CI]: 1.00–1.18; P = 0.048). In the uFSH group, the pregnancy rate was negatively correlated with the progesterone level on the day of HCG administration, with an OR of 0.47 (95% CI: 0.27–0.77; P = 0.004). Our research concluded that uFSH performed better than rFSH in terms of pregnancy rates when it was associated with the GnRH antagonist protocol. Meanwhile, no significant differences in the rate of live births were observed between the two groups.

Gonadotrophins for ovulation induction in women with polycystic ovary syndrome.

Gonadotrophins for ovulation induction in women with polycystic ovary syndrome.

Random urinary gonadotropins as a useful initial test for girls with central precocious puberty.

Recent evidence indicates that urinary gonadotropins may be an alternative method for detecting pubertal disorders. The aim of this study was to evaluate the associations of first morning voided (FMV) and random urinary gonadotropins with the pubertal response to a gonadotropin-releasing hormone (GnRH) stimulation test to determine whether random urinary gonadotropins can be used as an alternative method for evaluating central precocious puberty (CPP). In total, 100 girls aged 6.0-8.9 years were enrolled. The subjects were divided into two groups according to their pubertal response to the GnRH stimulation test: a positive group (n = 68) and a negative group (n = 32). Random urinary luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH:FSH ratio were significantly positively correlated with FMV urinary LH (r = 0.411, p < 0.001), FMV urinary FSH (r = 0.494, p < 0.001), and the FMV urinary LH:FSH ratio (r = 0.519, p < 0.001). The optimal cutoff values from receiver operating characteristic (ROC) curve analyses were determined to be 0.20 IU/L for random urinary LH (area under the curve (AUC) of 0.812, p < 0.001), 3.03 IU/L for random urinary FSH (AUC of 0.670, p = 0.004) and 0.08 for the random urinary LH:FSH ratio (AUC of 0.784, p < 0.001). No differences were observed between FMV and random urinary LH (p = 0.827), between FMV and random urinary FSH (p = 0.650), or between the FMV and random urinary LH:FSH ratio (p = 0.688) in ROC curve analyses with DeLong's test. Based on our findings, random urinary gonadotropins may be applicable in clinical practice as a useful initial test for girls with CPP.

Total flavonoid contents in bamboo diets and reproductive hormones in captive pandas: exploring the potential effects on the female giant panda (Ailuropoda melanoleuca).

Phytoestrogens have been shown to affect the reproductive hormone levels in both humans and animals. As the main category of phytoestrogens, total flavonoids have a particularly important impact on female animals. To investigate the potential relationship between the total flavonoids in bamboo and the reproductive hormones in female giant pandas, urinary samples and dietary bamboo samples were collected from three main breeding locations (Beijing, Shaanxi and Sichuan). The chemical constituents of the total flavonoids in the bamboo were analysed and quantified using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Estradiol (E2), progestin (P), testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were measured via radioimmunoassay (RIA). The results revealed that the total flavonoids in the bamboo from Sichuan were significantly higher than those in the bamboo from Beijing and Shaanxi, and the concentration in bamboo from Shaanxi was higher than that from Beijing (P < 0.05). The urinary E2, P, T, FSH and LH levels in pandas from Beijing were significantly lower than those in pandas from Sichuan and Shaanxi (P < 0.05). The concentrations of six reproductive hormones were positively associated with the total flavonoid contents in bamboo. In addition, the birth rate of pandas in Sichuan was significantly higher than the birth rate of pandas in Beijing and Shaanxi (P < 0.05). Thus, the flavonoids of bamboo may be related to reproduction and giant pandas might retain a sensitive adaptation to phytoestrogens from bamboo. The total flavonoids of bamboo may play a distinct role in the reproductive success of giant pandas.

Variation of urinary follicle-stimulating hormone level after menopause : From the results of Japan Nurses' Health Study.

The change in follicle-stimulating hormone (FSH) during the menopausal transition and associations of FSH with various diseases have been assessed by using blood samples. We examined cross-sectionally the variation of FSH levels, associations of estrone and estradiol with FSH, and associations of BMI with these hormones by using urinary samples from peri- and postmenopausal women in Japan. Of 4472 participants in the Urinary Isoflavone Concentration Survey of the Japan Nurses' Health Study, we analyzed urinary levels of estrone, estradiol and FSH in 547 women aged from 45 to 54 years. Urinary FSH levels varied widely in postmenopausal women and the pattern of change in urinary FSH levels seems to be similar to that in blood FSH levels in previous studies. There were no significant differences in age, body mass index (BMI), estradiol, estrone and estradiol/estrone ratio among three groups according to the tertile of FSH. In postmenopausal women, there were significant associations of BMI with levels of estrone and estradiol, but there was no significant association of BMI with FSH. Studies using urinary samples will allow us to establish a study project as a large-scale population-based study to determine associations between FSH and various diseases after menopause. J. Med. Invest. 66 : 297-302, August, 2019.

Use of clomiphene citrate alone, urinary follicle-stimulating hormone alone, or both combined sequentially in patients with unexplained subfertility undergoing intrauterine insemination: A randomized trial.

Objective:To compare the successes of clomiphene citrate (CC) alone, pure human urinary follicle-stimulating hormone (uFSH) alone, and both combined sequentially in patients with unexplained subfertility couples undergoing intrauterine insemination (IUI).Materials and Methods:Patients aged 18-38 years who had a normal uterine cavity, at least one normal fallopian tube, and regular menses and were unable to conceive despite unprotected intercourse for at least 12 months were randomized to receive CC alone, uFSH alone, or sequential CC and uFSH before a single IUI. The primary outcomes were clinical pregnancy and live birth rates. The study was approved by the ethics committee of our institution.Results:A total of 135 patients were randomized, and 121 of these were able to complete the study. Of these, 30% (n=36) had CC alone, 34% (n=41) had uFSH alone, and 36% (n=44) had sequential CC and uFSH. The three groups did not significantly differ in terms of age, duration of infertility, hormone levels, and semen parameters. For CC alone, uFSH alone, and sequential CC plus uFSH groups, pregnancy rates were 8.3%, 17.1%, and 18.2%, respectively (p>0.05), and live birth rates were 8.3%, 12.1%, and 13.6%, respectively (p>0.05).Conclusion:In women with unexplained infertility, use of uFSH seemed to increase the success rate compared with CC alone. The sequential regime can significantly reduce the treatment cost if gonadotropin/IUI cycles are planned.

Biosimilar FSH Preparations Versus Highly Purified Urinary FSH for Simple Ovulation Induction in Infertile Women with Polycystic Ovary Syndrome

Biosimilar FSH Preparations Versus Highly Purified Urinary FSH for Simple Ovulation Induction in Infertile Women with Polycystic Ovary Syndrome

PIH7 - LONG-ACTING RECOMBINANT FSH (CORIFOLLITROPIN ALFA) VERSUS RECOMBINANT FSH AS ASSISTED REPRODUCTION TECHNIQUES IN THE MANAGEMENT OF INFERTILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Assisted reproductive technologies (ARTs) are well-established treatments for many types of subfertility. Current treatment regimens prescribe daily injections of FSH (urinary FSH or recombinant FSH (rFSH)). Corifollitropin alfa (CRFa) is a new long-acting FSH which can replace seven daily FSH injections during the first week of controlled ovarian stimulation. This study was aimed to compare the effectiveness of CRFa versus rFSH in terms of pregnancy and safety outcomes in women undergoing ARTs. A systematic review was conducted in major databases including PubMed, Cochrane, Embase, Google scholar, and Web of Science up to June 2018 with limitation to English full-text published articles. Data extraction and assessment of risk of bias was independently done by two review authors. Mantel-Henszel odds ratios (OR) and standardized mean differences (SMD) were calculated for outcomes. The primary outcomes were live birth rate, ovarian hyperstimulation syndrome (OHSS) rate, the number of oocytes retrieved, and the number of embryos transferred. Meta-analysis was performed using RevMan 5.3 software. The study examined nine RCTs including 2407 patients receiving CRFa and 2056 women receiving daily rFSH. Although women receiving CRFa had a significantly higher number of oocyte retrieved (SMD: +0.25 , 95%CI: 0.11-0.39 ), number of metaphase II oocytes (SMD: +0.28 , 95%CI: 0.11-0.44 ), and number of embryos obtained (SMD: +0.27 , 95%CI: 0.13-0.41), in comparison to rFSH; there was a significant differences in the rate of embryos transferred in favor of rFSH (OR: 0.68, 95%CI: 0.55–0.85). However, no significant differences between CRFa and rFSH was found with respect to the majority of clinical effectiveness and safety parameters considered including live birth rate, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and OHSS rate. A single dose of CRFa for the first 7 days of ovarian stimulation is a generally well-tolerated and equally effective treatment compared with rFSH.