Follicle-stimulating Hormone Concentrations Research Articles

Direct effect of RFRP‑3 microinjection into the lateral ventricle on the hypothalamic kisspeptin neurons in ovariectomized estrogen‑primed rats

RFamide-related peptide-3 (RFRP-3) may be involved in the inhibition of kisspeptin, but there is no direct evidence that RFRP-3 can directly act on kisspeptin neurons. The present study aimed to investigate the role and mechanism of RFRP-3 and kisspeptin in the hypothalamic-pituitary reproductive axis. In order to detect the expression and localization of RFRP-3 and kisspeptin in dorsomedial hypothalamic nucleus, double immunofluorescence method combined with confocal microscopy were performed. RFRP-3 was injected into the lateral ventricle of ovariectomized estrogen primed rats. Blood and brain tissues were collected at 60-, 120-, 240- and 360-min. Serum levels of gonadotropin-releasing hormone, luteinizing hormone and follicle-stimulating hormone were detected by ELISA. Kisspeptin expression in hypothalamus was detected by western blotting. Finally, surface plasmon resonance was used to verify whether RFRP-3 can directly interact with kisspeptin. Confocal images indicated that RFRP-3 and kisspeptin were co-expressed in the same neurons in the hypothalamus of ovariectomized estrogen-primed rats. Serum concentrations of gonadotropin-releasing hormone, luteinizing hormone and follicle-stimulating hormone were demonstrated to be significantly reduced following microinjection of RFRP-3 into the lateral ventricle for 60, 120, 240 and 360 min compared with the corresponding saline groups. The expression levels of kisspeptin in hypothalamus were gradually decreased following microinjection of RFRP-3 into the lateral ventricle. In addition, the affinity constant (KD) of RFRP-3 binding to kisspeptin was 6.005x10-5 M, indicating that RFRP-3 bound directly to kisspeptin in the range of protein-protein binding strength (KD, 10-3-10-6 M). In conclusion, RFRP-3 may regulate the hypothalamic-pituitary reproductive axis by inhibiting the expression of hypothalamic kisspeptin and direct binding.

Effects of ammonia on hypothalamic-pituitary-ovarian axis in female rabbits

BackgroundAs one of the most harmful gases in the livestock house, ammonia is recognized as an environmental stressor by Environmental Protection Agency (United States). The study aimed to explore the effect of ammonia on hypothalamic-pituitary-ovarian (HPO) axis of rabbits. A total of ninety two-month-old female IRA rabbits were randomly divided into three groups, and were kept in animal environment control rooms for four weeks at college of animal science and technology, Hebei Agricultural University (Baoding, China). The rabbits in the control group were kept under ammonia concentration of < 3 ppm. The two treatment groups were kept under ammonia concentration of 30 ppm and 50 ppm. Hypothalamus, pituitary, and ovary were collected for hematoxylin and eosin (HE) staining, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Serum was collected for enzyme-linked immunosorbent assay (ELISA). ResultsHistopathological examination revealed that exposed to excess ammonia damaged the morphology and structure of hypothalamus, pituitary, and ovary. TUNEL assay revealed that apoptosis rate increased in hypothalamus, pituitary, and ovary. The protein expression levels of Bcl-2associated X protein (Bax) and Caspase-9 increased, while B-cell lymphoma-2 (Bcl-2) decreased, resulting in apoptosis. Moreover, the concentration of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (PROG) reduced in plasma. The mRNA expression of FSH and LH in pituitary and follicle-stimulating hormone receptor (FSHR), E2, PROG in ovary as well as decreased, indicated hormone secretion disorder. ConclusionsThe results indicated that ammonia exposure damaged hypothalamus, pituitary, and ovary, caused hormone secretion disorder and apoptosis.

Assessment of Growth and Fertility Hormones of Albino Rats Exposed to Quarry Dust at a Quarry Industry

Aim: Growth and fertility hormones of albino rats exposed to quarry dust were evaluated to determine if the inhaled quarry dust and heavy metals contained in it have any effect on the fertility and growth of the rats.&#x0D; Methods: Sixty (30 in each of wet and dry seasons) male albino rats were used in this study and were housed in six (6) sterilized plastic cages with five (5) rats in each cage at Ugwuele quarry industry Uturu. The control (group 1) was housed at a distance of 7.2km from the quarry site. Group 2 was housed at the administration block of the quarry industry while groups 3,4,5,6 were housed at the gate, plant house, drilling pit and crusher positions of the quarry industry respectively. Heavy metals; lead, chromium, cobalt, arsenic, zinc and cadmium from dust samples were analyzed with atomic absorption spectrophotometer while assay for hormones was also carried out using standard analytical methods.&#x0D; Results: All the analyzed heavy metals were present in the dust. Concentrations of heavy metals in the quarry dust were significantly higher (p&lt;0.05) than the control and higher in the dry season than in the wet season. Concentrations of prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) in the test samples were significantly lower (p&lt;0.05) compared to the control while the concentrations of thyroid stimulating hormone (TSH) in the test samples were significantly higher (p&lt;0.05) compared to the control. Results also show that the concentrations of prolactin, FSH, LH and GH were lower in the dry season than in the wet season whereas, the concentrations of TSH in the exposed rats were higher in the dry season than in the wet season. &#x0D; Conclusion: Growth rate and fertility of the albino rats may have been compromised by the exposure to the quarry dust, since the growth and fertility hormones were all reduced.

Association between Bovine GDF9 SNPs and Calving Rate (Superovulation) in Holstein-Friesian Cows.

The present study aimed to assess the relationship of Growth Differentiation Factor 9 (GDF9) genotypes with calving rate, Follicle-stimulating hormone (FSH), and Estradiol (E2) in the Iraqi Holstein-Friesian breed. A number of 15 blood samples were collected from a mother of dizygotic twin birth (DZTB) (with high calving rate records), and another blood sample was collected from 15 single birth (SB) cows. The DNA was extracted and six primers were designed for PCR and sequencing analysis. The FSH and E2 levels were tested through the estrus phase for the two groups (n=10 in each group). The sequence evaluation revealed the presence of two single nucleotide polymorphisms (SNPs) in exon II: A (1109) T and G (1133) A.The genotypic frequency for mutant genotypes was higher significantly (P<0.01) in DZTB cows (with calving rate), as compared to wild genotypes at the same loci. On the other hand, the wild genotypes recorded a significant increment (P<0.01) for SB cows, when compared to mutant genotypes in the same loci. Moreover,a significant rise (P<0.05) was reported in E2 and FSH levels for DZTB cows and mutant genotypes(P<0.01) against SB cows and wild genotypes in 0 and 24 h of estrus phase, respectively. Furthermore, non-significant differences were recorded in E2 concentration among the same genotypes at the same period.In conclusion, the GDF9exon II SNPs increased the calving rate in Holstein-Friesian cows. The blood FSH and E2 concentrations were higher in the DZTB cows and control the superovulation. Finally, these SNPs can be regarded as markers to accelerate the breeding programs and used in embryo transfer and in vitro embryo production for Iraqi Holstein-Friesian cow breed.

Lack of pharmacokinetic interaction between the HIV-1 maturation inhibitor GSK3640254 and combination oral contraceptives in healthy women.

AimsGSK3640254 is a next‐generation maturation inhibitor likely to be coadministered with combined oral contraceptives in HIV‐positive women.MethodsThis phase I, open‐label, 1‐way study assessed pharmacokinetic and pharmacodynamic interactions of GSK3640254 200 mg and ethinyl oestradiol 0.03 mg/levonorgestrel 0.15 mg once daily in healthy female participants who received ethinyl oestradiol/levonorgestrel for 10 days with a moderate‐fat meal after which GSK3640254 was added from Days 11 to 21. Primary endpoints were area under the plasma concentration–time curve to the end of the dosing interval (AUC0‐t), maximum observed concentration (Cmax) and plasma concentration at the end of the dosing interval (Cτ) for ethinyl oestradiol and levonorgestrel. Serum follicle‐stimulating hormone, luteinizing hormone and progesterone concentrations were determined. Adverse events were monitored.ResultsAmong 23 enrolled participants, 17 completed the study. Geometric least squares mean ratios (with vs. without GSK3640254) of AUC0‐t, Cmax and Cτ were 0.974, 0.970 and 1.050 for ethinyl oestradiol and 1.069, 1.032 and 1.083 for levonorgestrel, respectively. Three participants had elevated progesterone levels, which occurred before GSK3640254 administration in 2 participants. No participants had elevated follicle‐stimulating hormone or luteinizing hormone values. Fourteen participants (61%) reported adverse events. Four participants reported asymptomatic elevated transaminase levels meeting liver‐stopping criteria; of these, 3 events occurred before GSK3640254 administration and led to study withdrawal.ConclusionEthinyl oestradiol/levonorgestrel plus GSK3640254 coadministration did not affect steady‐state pharmacokinetics or pharmacodynamics of ethinyl oestradiol and levonorgestrel in healthy female participants. No major tolerability findings were reported. Elevated liver transaminase levels were probably due to ethinyl oestradiol/levonorgestrel.

Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice

BackgroundCurrently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF.MethodsFemale mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy.ResultsOvary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group.ConclusionThese results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.

Triphenyl phosphate delayed pubertal timing and induced decline of ovarian reserve in mice as an estrogen receptor antagonist

Although concerns have been raised about the adverse effects of triphenyl phosphate (TPhP) on female fertility, its risk to ovarian functioning remains unknown. In this study, female C57BL/6 mice at postnatal day 21 were exposed on a daily basis to TPhP dose of 2, 10, and 50 mg/kg for 40 days. A significant delay in pubertal timing was observed in the mice exposed to 50 mg/kg of TPhP. An estrogen-responsive reporter transgenic mice assay demonstrated that TPhP significantly downregulated the estrogen receptor (ER) signaling by 45.1% in the whole body in the 50 mg/kg group, and by 14.7–43.7% in the uterus for all exposure groups compared with the control. This strong antagonistic activity of TPhP toward ER explained the delay in pubertal timing. A significant reduction in the number of follicles in all stages was observed in mice after being exposed to TPhP for 40 days at concentrations of 10 and 50 mg/kg, resulting in a decline of the ovarian reserve. The elevation of the follicle-stimulating hormone concentration may have contributed to this phenomenon, as controlled by the antagonistic activity of TPhP toward ER in the brain. The toxic effects of TPhP on ovarian functioning highlight this chemical as a potential risk factor for female fertility.

Immunohistochemical examination of androgen receptor and estrogen receptor alpha expressions in obstructive and non-obstructive azoospermia

ABSTRACT In this study, the expression of the androgen receptor (AR) and estrogen receptor alpha (ERα) in testicular tissue of male patients with obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) were evaluated by immunohistochemistry. NOA (n = 23) and OA (n = 21) groups were created according to clinical and laboratory archival records. Testicular sperm extraction tissue sections were evaluated according to Johnsen’s tubular biopsy scoring (JTBS) method. ERα and AR immunostaining results were evaluated semiquantitatively. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and estradiol were analyzed. Serum FSH and LH concentrations were greater, and testosterone concentrations were lower than the normal values in the NOA group, whereas the OA group revealed normal hormonal values. Serum estradiol concentrations in groups were in the normal range. JTBSs were significantly lower in the NOA group. Decreased AR expression and increased ERα expression were observed in the NOA group compared to the OA group. This suggests that ERα and AR are expressed in Sertoli cells, Leydig cells, and myoid cells and are required for normal testicular function. Decreased expression of the AR and increased expression of ERα in the testis may negatively affect spermatogenesis. Abbreviations: AR: androgen receptor; ER: estrogen receptor; ERα: estrogen receptor alpha; FSH: follicle-stimulating hormone; JTBS: Johnsen’s tubular biopsy scoring; LH: luteinizing hormone; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; TESE: testicular sperm extraction

Transcriptome analysis reveals key genes and pathways associated with egg production in Nandan-Yao domestic chicken

BackgroundEgg production is a very important economic trait in chicken breeding, but its molecular mechanism is unclear until now. Nandan-Yao chicken (Gallus gallus domesticus) is a native breed in Guangxi province, China, which is famous for good meet quality, but with low egg production. MethodsTo explore the molecular regulation related to egg production, high egg production (HEP) and low egg production (LEP) were divided according to the total egg number at 55 weeks, and the concentration of serum sex hormones was tested to evaluate the physiological function of ovary and uterus. RNA sequencing (RNA-Seq) was used to explore the transcriptome from the ovary and uterus of Nandan-Yao chicken. ResultsThe levels of serum sex hormone showed that concentrations of estradiol (E2), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were significantly higher in HEP than those in LEP (P < 0.01), while the concentration of testosterone (T) was significantly lower in HEP (P < 0.01). RNA-Seq analysis identified 901 and 2763 differentially expressed genes (DEGs) in ovary and uterus, respectively. Enrichment analysis showed that DEGs were significantly involved in the regulation of tight junction in the ovary (P < 0.05), while in uterus, DEGs were mainly enriched in the phagosome, ECM-receptor interaction, cell adhesion molecules (CAMs), focal adhesion, cardiac muscle contraction, cytokine-cytokine receptor interaction, and the regulation of MAPK signaling pathway (P < 0.05). Protein network interaction and function analyses revealed that FN1, FGF7, SOX2 identified from the ovary, and UQCRH, COX5A, FN1 from the uterus might be key candidate genes for egg production in Nandan-Yao chicken. ConclusionsOur study provided key candidate genes and pathways involved in the egg-laying process of Nandan-Yao chicken and could help to further understand the molecular mechanisms of chicken reproduction.

Effect of chronological age of patients with diminished ovarian reserve on in vitro fertilization outcome

The aim of this study was to evaluate the effect of chronological age on the in vitro fertilization (IVF) outcome in patients with diminished ovarian reserve (DOR). Four hundred and forty-nine women with DOR who underwent IVF cycles were enrolled in the study. There were only 296 patients who obtained available embryos. The patients with no available embryos had a significantly lower antral follicle count (AFC) and higher basal follicle-stimulating hormone (FSH) concentrations than those of women with available embryos, but chronological age in the two groups was comparable. However, patients aged >40 obtained a significantly lower ongoing pregnancy rate (OPR) than patients aged 35 − 40 or <35 (6.38% versus 26.15% versus 28.17%, respectively). Multivariate analysis also showed that chronological age was the only parameter associated with clinical results. It implied that patients with DOR still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Impact statement What is already known on this subject? Diminished ovarian reserve DOR is a disappointing issue in reproductive medicine. Ovarian reserve, which represents ovarian biological age, is closely related to chronological age. However, ovarian biological age does not always match chronological age. Some studies suggest that biological age is more important than chronological age in predicting the outcome of in vitro fertilization (IVF). However, these conclusions are controversial. What do the results of this study add? We found DOR patients with no available embryos had significantly lower antral follicle count (AFC) and higher follicle-stimulating hormone (FSH) concentrations than that of patients with available embryos, but chronological age in the two groups was comparable. However, for patients with available embryos, chronological age is the only parameter associated with clinical results. For women aged >40 with DOR, chronological age was significantly negatively associated with clinical results. What are the implications of these findings for clinical practice and/or further research? Patients with DOR can obtain available embryos and still have a reasonable chance of becoming pregnant, but their prognosis is greatly affected by chronological age. Therefore, patients with DOR should seek medical help for pregnancy as soon as possible. When DOR patients over the age of 40 plan IVF treatment, the cost-effectiveness of healthcare should be considered.

P–650 Body weight is the main determinant of systemic follicle stimulating hormone (FSH) concentrations during controlled ovarian stimulation with follitropin delta

Abstract Study question Which individual subject characteristics affect systemic FSH concentrations in women undergoing controlled ovarian stimulation with follitropin delta? Summary answer Body weight is the main determinant of systemic FSH concentrations. Renal function, Asian race, country/region, hepatic function and age have at most a small influence. What is known already After administration of FSH, systemic FSH concentrations are inversely related to body weight. It has been observed that the impact of body weight on ovarian response is clinically relevant at low doses but not at high doses. In patients with anti-Müllerian hormone (AMH) ≥15 pmol/L, follitropin delta is dosed according to each patient’s body weight, which influences systemic FSH concentrations, and her AMH level which predicts ovarian response. Study design, size, duration Serum FSH concentrations were assessed in five randomised, controlled, assessor-blinded, multicentre trials of follitropin delta in women undergoing an assisted reproductive technology programme. The trials were conducted in Europe, America and Asia. In all, 1.665 women treated with follitropin delta contributed to the evaluation with 4052 serum FSH concentrations, measured at steady state by an immunoassay. Participants/materials, setting, methods FSH concentrations were described with a pre-specified one-compartment population pharmacokinetic model. The key model parameters were the apparent total clearance (CL/F) of follitropin delta, the interindividual variability herein and the effects of baseline values of body weight, age, race, country/region, renal and hepatic function on CL/F. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and hepatic function by alanine transaminase (ALT) and bilirubin levels. Main results and the role of chance The area under the FSH concentration-time curve during a dosing interval (AUC) was derived from dose and CL/F. Body weight was the covariate with the most pronounced effect on AUC, both in terms of the effect magnitude and statistical significance. AUC was 1.51-fold higher (90% confidence limits: 1.48; 1.54) in women with the lowest observed body weight of 40 kg compared to women with a typical body weight of 58 kg. The effect of renal function on AUC was small and in the same order of magnitude as the bioequivalence limits (0.8; 1.25). AUC was 1.28-fold higher (90% confidence limits: 1.23; 1.33) in women with the lowest observed eGFR value of 44 mL/min/1.73m2, compared to women with a typical eGFR value of 98 mL/min/1.73m2. The effects of Asian race and country/region (Japan, China, Other Asian) were confounded with each other and well within the bioequivalence limits when evaluated independently. The effects of age and the hepatic function markers ALT and bilirubin were well within the bioequivalence limits. Limitations, reasons for caution The women participating in the trials were generally healthy and the results cannot be transferred to women with renal or hepatic disease. A limited number of Black women contributed to the present analysis but the trend was similar. Data is forthcoming from ongoing trials including larger numbers of Black women. Wider implications of the findings: The findings support dosing follitropin delta by body weight and without adjustment for renal function, hepatic function, race, age or country/region. Trial registration number NCT01426386, NCT02309671, NCT01956110, NCT03228680 and NCT03296527

O-229 Impact of letrozole co-treatment during ovarian stimulation with gonadotropins for in vitro fertilisation (IVF): a multicentre, randomised, double-blinded placebo-controlled trial

Abstract Study question Does reducing estradiol levels with letrozole co-treatment during ovarian stimulation with gonadotropins for IVF impact endocrinological and reproductive outcome markers in expected normal responders? Summary answer Letrozole co-treatment maintained follicular phase physiological serum estradiol levels, increased gonadotropin and androgen levels, and increased progesterone in the luteal phase. What is known already Ovarian stimulation for IVF causes supraphysiologic estradiol levels, which exert pituitary suppression reducing gonadotropin stimulation of the corpus luteum. Furthermore, stimulation may increase progesterone in the late follicular phase, reported to impair clinical outcomes, through a putative effect on endometrial maturation and embryo-endometrial asynchrony. Co-treatment with the highly selective aromatase inhibitor letrozole during ovarian stimulation has been shown to reduce estradiol levels and FSH consumption in poor responders, but conflicting data in relation to oocyte yield and implantation rates. The impact of letrozole co-treatment on hormonal changes and reproductive outcome after co-treatment in normal responders remains to be clarified. Study design, size, duration A multicentre double-blinded randomised placebo-controlled trial conducted in 4 fertility clinics at university hospitals in Denmark from August 2016 to November 2018. 159 women were randomised and 129 completed the study; 67 women in the letrozole group and 62 women in the placebo group. The study was conducted in accordance with the Helsinki Declaration and the ICH-Good-Clinical-Practice. Data collection and reporting followed the guidelines of CONSORT to achieve transparent reporting of trials. Participants/materials, setting, methods Women with expected normal ovarian reserve received an antagonist IVF protocol with fixed-dose FSH and fresh single embryo transfer. Co-treatment consisted of once-daily 5 mg letrozole or placebo from the start of stimulation until the day of triggering final oocyte maturation with human chorionic gonadotropin. Serum was collected on 7 visits from stimulation start to 8 days after oocyte retrieval. Clinical pregnancy was determined with a viable foetus by vaginal ultrasound at gestational week 7. Main results and the role of chance The proportion of patients with progesterone &amp;gt;1.5 ng/ml in the late follicular phase was similar in the letrozole versus placebo group with 6% versus 0%, respectively (OR 0, 95 % CI [0;1.6], P =.12). Mid-luteal progesterone levels &amp;gt;30 ng/ml were observed in 59% versus 31%, respectively, of subjects in the letrozole and placebo group (OR 3.3, 95% CI [1.4;7.1], P =.005). Letrozole treatment decreased estradiol levels by 69% (95 % CI [60%;75%], P &amp;lt;.0001) and increased luteinizing hormone (LH), testosterone, and androstenedione levels significantly in both the follicular and luteal phase. Follicle-stimulating hormone (FSH) concentration was elevated in the letrozole group at stimulation day 5 and at trigger day, and overall FSH consumption was diminished. The ongoing pregnancy rate did not differ between the letrozole and placebo group (31% versus 39% (risk-difference of 8%, 95% CI [-25%;11%], P =.55). Letrozole had no significant additional side effects apart from those frequently seen during ovarian stimulation, though a trend towards less nausea and vomiting was observed in the letrozole co-treated group versus the placebo group (28% versus 44% (risk-difference of 16%, 95% CI [-2%;33%], P =.11). Limitations, reasons for caution The diurnal variation of progesterone has been confirmed since this study was completed, hence the timing of the blood samples was not standardized . However, bias is unlikely due to the randomized design. The study was not powered to show an effect on ongoing pregnancy rates. Wider implications of the findings Letrozole co-treatment during ovarian stimulation with gonadotropins maintained serum estradiol at physiological levels, increased follicular phase levels of gonadotropins and androgens, and luteal progesterone levels. These data indicate that letrozole co-treatment may ameliorate the detrimental impacts of gonadotropin stimulation during IVF in normal responders. Trial registration number NCT02939898 and NCT02946684

O-173 Decline in anti-Müllerian hormone (AMH) concentrations following radioactive iodine (RAI) treatment in women with differentiated thyroid cancer (DTC): a systematic review and meta-analysis

Abstract Study question Does radioactive iodine (RAI) treatment in premenopausal women with differentiated thyroid cancer (DTC) affects ovarian reserve, as evaluated by anti-Müllerian hormone (AMH), antral follicle count (AFC) and follicle-stimulating hormone (FSH)? Summary answer AMH concentrations decreased at three, six and 12 months following RAI treatment in women with DTC, whereas no difference was observed regarding FSH. What is known already Thyroid cancer is the third most common type of female malignancy and DTC is the most common histopathological type. Thyroidectomy constitutes the mainstay of treatment for DTC, followed by administration of RAI, which acts as an adjuvant therapy to destroy residual cancerous thyroid tissue. However, the effect of RAI on ovarian reserve of these women, as assessed by AMH, AFC and FSH, remains controversial. Study design, size, duration A systematic review and meta-analysis was performed aiming to identify studies evaluating the effect of RAI treatment on ovarian reserve in women with DTC. For this purpose, a literature search in the electronic databases PubMed, Scopus and CENTRAL was carried out until 06/12/2020. The primary outcome measure was the effect of RAI on ovarian reserve, as evaluated by AMH, AFC and FSH. Participants/materials, setting, methods Studies were eligible if they included premenopausal women with DTC, treated with a single RAI dose and assessed for at least one marker of ovarian reserve repeatedly within 12 months post-RAI.Meta-analysis of weighted data was performed using random effects model. Results were reported as weighted mean difference (WMD) with 95% confidence interval (CI). Main results and the role of chance Four prospective eligible studies, published between 2005 and 2020, were eligible for the meta-analysis, evaluating a total of 154 women. The number of participants ranged from 24 to 50. The single dose of RAI used to treat DTC ranged from 50 to 150 mCi. AMH concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p &amp;lt; 0.0001; I2 0%), six (WMD -1.58 ng/ml, 95% CI -2.63 to -0.52, p = 0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p &amp;lt; 0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n = 104). With respect to FSH concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to + 7.70, p = 0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to + 1.32, p = 0.83; I2 55.2%) post-RAI compared with baseline (two studies; n = 83). No data on AFC was available. Limitations, reasons for caution The small number of studies and patients included, as well as the lack of data on AFC may have compromised the validity of the conclusions drawn. Moreover, subgroup analysis according to female age was not feasible, due to the lack of relevant data. Wider implications of the findings The negative effect of RAI on ovarian reserve in premenopausal women with DTC, as indicated by the decreased AMH, should be confirmed by data on AFC, which are currently not available. These findings necessitate close monitoring of ovarian reserve in such women, counselling them regarding the need for fertility preservation. Trial registration number N/A

Endocrine Follow-Up of Men with Non-Obstructive Azoospermia Following Testicular Sperm Extraction.

Testicular sperm extraction (TESE) is a surgical procedure which, combined with intracytoplasmic sperm injection, constitutes the main treatment for achieving biological parenthood for patients with infertility due to non-obstructive azoospermia (NOA). Although it is effective, TESE procedures might cause structural testicular damage leading to Leydig cell dysfunction and, consequently, temporary or even permanent hypogonadism with long-term health consequences. To a lesser extent, the same complications have been reported for microdissection TESE, which is considered less invasive. The resulting hypogonadism is more profound and of longer duration in patients with Klinefelter syndrome compared with other NOA causes. Most studies on serum follicle-stimulating hormone and luteinizing hormone concentrations negatively correlate with total testosterone concentrations, which depends on the underlying histology. As hypogonadism is usually temporary, and a watchful waiting approach for about 12 months postoperative is suggested. In cases where replacement therapy with testosterone is indicated, temporary discontinuation of treatment may promote the expected recovery of testosterone secretion and revise the decision for long-term treatment.

Serum gonadotropins, cortisol, PSA, and micronutrient levels among men with prostate carcinoma

BackgroundProstate cancer (PrCa) is a malignant tumour of the prostate that has many associated risk factors. There is continuous rise in the incidence among adult blacks which is a reflection of racial differences in testosterone concentrations.MethodsThe study involves 50 PrCa patients attending or referred to two tertiary health Institutions and 25 healthy men as controls. Weight and height of participants were measured, and body mass index (BMI) was calculated. Ten millilitres of venous blood sample was collected from each participant, allowed to clot, and then centrifuged at 5000 rpm for 5 min at room temperature (22–28 °C) to obtain the serum. Serum cortisol, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total prostate-specific antigen (TPSA), free prostate-specific antigen (FPSA), selenium, copper, magnesium, and zinc were determined. Prostate ultrasonography and biopsy were also done for histopathological studies.ResultFrom this study, a significant increase (p < 0.05) in weight, BMI, serum FPSA, TPSA, and copper; a non-significant increase (p > 0.05) in serum cortisol, testosterone; a significant decrease (p < 0.05) in serum LH, selenium, zinc, and magnesium; and a non-significant decrease (p > 0.05) in serum FSH were observed among people living with PrCa when compared to the controls. However, no significant difference (p > 0.05) was observed in the height between the two groups. Ultrasonography and histology revealed evidence of prostatitis, hypertrophy, and carcinoma among the test group.ConclusionIt can be concluded that PrCa is associated with increase serum cortisol, testosterone, and copper; and decreased serum LH, FSH, selenium, zinc, and magnesium concentrations and combination of biochemical, ultrasonographic, and histologic features are of diagnostic importance.

Effects of a Recombinant Gonadotropin-Releasing Hormone Vaccine on Reproductive Function in Adult Male ICR Mice.

Gonadotropin-releasing hormone (GnRH) regulates the reproductive endocrine system in mammals. The GnRH immunocontraception vaccine can aid animal population control and management. We evaluated a recombinant GnRH fusion protein with the adjuvant MONTANIDE ISA 206 VG as a GnRH vaccine in adult male ICR mice by evaluating anti-GnRH antibodies; concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone; testis size and histomorphology; and semen quality. Response was assessed after intramuscular administration of the vaccine to mice in weeks 0, 4, and 8. The vaccine induced specific antibody response by week 5, with peak of antibody levels observed by week 13 and a declining level thereafter until the end of the study at week 24. Furthermore, it reduced serum FSH, LH, and testosterone concentrations. The vaccinated mice exhibited testicular atrophy and reduced sperm quality, concentration, morphology, and viability compared to control males. The outcomes of pairings of treated males with untreated females revealed reduced mating, pregnancy rates and number of litters compared to control pairings. Assessment of this GnRH vaccine in different species could assist its development for future applications.

Effect of FSH and eCG on Alpaca (Vicugna pacos) Oocyte Maturation in vitro

This study evaluated alpaca oocytes that developed to metaphase II (MII), using different concentrations of follicle stimulating hormone (FSH) with and without equine chorionic gonadotropin (eCG) during in vitro maturation. Oocytes were obtained from ovaries of slaughtered alpacas. Oocytes were matured in vitro for 36h in TCM-99 and supplemented in groups with different doses of FSH: 0.5, 0.25, 0μg.mL-1 and eCG: 15, 5, 0IU.mL-1. Oocytes were stained with 2% lacmoid, and examined for their nuclear status. The parameter for comparisons between groups was the percentage of oocytes in MII. There was an interaction between FSH and eCG (P&lt;0.05). A higher percentage of oocytes in MII were obtained when using 0.5µg.mL-1 of FSH with any concentration of 15, 5 or 0IU.mL-1 of eCG [58.4±1.94% (n=78); 59.5±1.94% (n=85); 54.3±0.56% (n=81); P&lt;0.05]. A similar percentage was also found using 0.25µg.mL-1 of FSH plus 15IU.mL-1 of eCG [52.3±1.66% (n=86); P&gt;0.05] followed by 0.25µg.mL-1 of FSH with 5 or 0IU.mL-1 of eCG [47.3±1.94% (n=82); 45.3±1.94% (n=86); P&lt;0.05]. The lowest maturation percentages were found using any concentration of eCG without FSH [8.2±0.73% (n=84); 8.0±0.66% (n=74); 11.4±1.23% (n=71); P&lt;0.05]. In conclusion, the addition of eCG to the maturation medium would reduce the amount of FSH required in the in vitro maturation of alpaca oocytes.

Effect of Thymus vulgaris leaf extract on cadmium-induced testicular toxicity in rats

BackgroundCadmium (Cd) is a known metallohormone which mimics the action of steroid hormones with adverse effect on testicular function. It is highly toxic and a prevalent environmental contaminant with no conventional antidote. This study investigates the possible ameliorative effects of Thymus vulgaris extract on testicular toxicity induced by Cd in male rats.ResultsThe testicular and epididymal weights, serum concentration of follicle stimulating hormone, luteinizing hormone, and testosterone were significantly (p ≤ 0.05) lower in the cadmium-treated group compared to the control. Necrosis of germ cells of the seminiferous tubules was observed in the testicular tissues of the cadmium-treated group. Administration of extract showed mild but non-significant (p ≥ 0.05) protective effect on the cadmium-induced decrease in sex hormones and sperm count as well as oxidative stress and histological changes.ConclusionThymus vulgaris leaf extract had weak ameliorative effect on cadmium-induced testicular injury in rats but with promising antioxidant activity.

Proposed age-stratified reference intervals of FSH derived from normozoospermic men

Objective: To demonstrate that serum follicle-stimulating hormone (FSH) in men rises with age, and to explore FSH reference intervals of age-related partitioning. Methods: Men aged 20-50 years (n=1 190) underwent semen analysis according to World Health Organization (2010) methods. Serum was frozen prior to measurement of FSH by using the Siemens ADVIA Centaur® XP immunoassay system. FSH central 95% intervals after logarithmic transformation based on age were derived from 1 037 normozoospermic men. These were then applied to oligozoospermic and azoospermic men. Men producing azoospermic semen samples were further classified as having non-obstructive azoospermia by clinical diagnostic criteria, including genetic analysis and surgical exploration. Results: Serum FSH in normozoospermic men increased with age (P&lt;0.05), and reference intervals were determined with 10-year brackets: 21-30 years [(1.0-8.2) IU/L], 31-40 years [(1.4-9.5) IU/L], 41-50 years [(1.9-12.0) IU/L]. The proportion of oligozoospermic men with normal FSH concentrations was less than the normozoospermic men, which in turn was lower among azoospermic men (both P&lt;0.01). The azoospermic men were further broken down according to the nature of the azoospermia as either obstructive or non-obstructive azoospermia, and 86.4% (38/44) men with non-obstructive azoospermia had elevated serum FSH concentrations whereas only 6.7% (1/15) men with obstructive azoospermia had high FSH levels, and this was significantly different (P&lt;0.01). Conclusions: FSH concentrations increase in men between 20-50 years, and clinical interpretation of serum FSH results in men must be made by using age-based reference intervals.

Study of the effect of prolactin on FSH and LH hormones and fertility in women in Tocra – Libya

The prolactin hormone (PRL) has a distinct activity among the rest of the hormones, so this study conducted to measure the level of this hormone and its relationship with Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). The study performed on a group of 30 women with a wide age range in the city of Tocra (east of Benghazi) to find out the percentage of PRL hormone and the extent of its effect on the FSH And LH hormones, as well as on fertility in these women. The results showed that 24 samples of the total samples, with a rate of 80%, had a normal concentration of PRL hormone, and 6 samples of the total samples, and by 20%, suffered an increase in the concentration of the PRL hormone. The concentration of FSH and LH was measured for the same samples for which the PRL hormone was measured, and the statistical analysis using the T test at significant values ​​(P &lt;0.05) showed that prolactin has a clear significant effect on the luteinizing hormone, while it has a slight effect of a non-significant value on the FSH. . Likewise, for average ages with FSH, LH, and PRL, there were strong significant differences between all hormones and age. This study concluded that the high PRL hormone might be a cause of delayed childbearing through its effect on the FSH hormones.