Pubertal development and reproductive hormone levels of singleton ICSI offspring in adolescence: results of a prospective controlled study

2020 ◽  
Vol 35 (4) ◽  
pp. 968-976 ◽  
Author(s):  
B Sonntag ◽  
N Eisemann ◽  
S Elsner ◽  
A K Ludwig ◽  
A Katalinic ◽  
...  

Abstract STUDY QUESTION Are there any differences in the pubertal development and reproductive hormone status during adolescence between singletons following ICSI therapy or spontaneous conception (SC)? SUMMARY ANSWER Pubertal development and reproductive hormone levels are largely similar between ICSI and SC adolescents, except for a tendency towards lower inhibin B levels as well as significantly higher estradiol levels and a lower testosterone-to-estradiol-ratio in male adolescents. WHAT IS KNOWN ALREADY Previous data are scarce and partly inconclusive regarding pubertal development in female ICSI adolescents as well as demonstrating a tendency towards lower inhibin B serum levels in male ICSI offspring. STUDY DESIGN, SIZE, DURATION Prospective controlled study including 274 singleton ICSI-conceived adolescents (141 girls, 133 boys) followed up for the third time, and 273 SC controls (142 girls, 131 boys) from seven German registration offices (Aachen, Eichstätt, Erfurt, Lübeck, Hamburg, Heidelberg and Schwerin). PARTICIPANTS/MATERIALS, SETTING, METHODS Pubertal development assessed by Tanner staging (breast, genital and pubic hair development), age at menarche and reproductive hormone levels were analyzed in ICSI and SC adolescents at the mean age of 16.5 years. Differences were analyzed by multinomial regression (Tanner stages) or t test and linear regression for hormonal assessments. MAIN RESULTS AND THE ROLE OF CHANCE Both female and male ICSI and SC adolescents showed adequate pubertal maturation according to their age, and the mean age at menarche (at 12.7 versus 12.8 years) was similar. Tanner stages as well did not display any relevant or significant differences between the groups. Reproductive hormone levels in female adolescents not using hormonal contraception were largely similar before and after adjustment for several factors such as preterm birth, Tanner stages, BMI or physical activity. In male ICSI adolescents, a tendency towards lower inhibin B (−14.8 pg/ml, 95% CI: −34.2 to 4.6 pg/ml), significantly higher estradiol (2.6 ng/l, 95% CI: 0.0 to 5.2 ng/l) and a significantly lower testosterone-to estradiol ratio (−0.047, 95% CI: −0.089 to −0.004) was found. LIMITATIONS, REASONS FOR CAUTION The all-over response rate and the willingness to participate in the blood test and medical examination were very low in the control group. Participating control families may have greater health awareness, and selection bias cannot be ruled out. Hormonal data in the females were measured irrespective of the cycle day and restricted to those not using hormonal contraception. Some parameters from the questionnaire data such as usage of hormonal contraception might suffer from reporting bias. As this is an observational study, we can draw only limited causal conclusions from the findings. WIDER IMPLICATIONS OF THE FINDINGS Differences in male reproductive hormones may indicate altered testicular function. However, at this time possible consequences for later reproductive success are unknown. STUDY FUNDING/COMPETING INTEREST(S) DFG research grant KA 1643/4-1. The authors declare no conflict of interest.

Author(s):  
Steve Pawsey ◽  
Edouard Gregory Mills ◽  
Elizabeth Ballantyne ◽  
Kirsteen Donaldson ◽  
Mary Kerr ◽  
...  

Abstract Context The ideal therapy for endometriosis (EM) and uterine fibroids (UF) would suppress estrogenic drive to the endometrium and myometrium, whilst minimizing vasomotor symptoms and bone loss associated with current treatments. An integrated neurokinin-kisspeptin system involving Substance P and neurokinin B acting at the neurokinin (NK) receptors 1 and 3, respectively, modulates reproductive hormone secretion and represents a therapeutic target. Objective To assess the effects of the novel NK1,3 antagonist elinzanetant on reproductive hormone levels in healthy women. Design Randomized, single-blinded, placebo-controlled study. Participants/Intervention Thirty-three women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum reproductive hormones. In cycle 2, women were randomized to receive once daily oral elinzanetant 40, 80, 120 mg or placebo (N=8 or 9 per group). Results Elinzanetant dose-dependently lowered serum luteinizing hormone, estradiol (120 mg median change across cycle: -141.4 pmol/L, P=0.038) and luteal phase progesterone (120 mg change from baseline on day 21/22: -19.400 nmol/L, P=0.046). Elinzanetant 120 mg prolonged the cycle length by median of 7.0 days (P=0.023). Elinzanetant reduced the proportion of women with a luteal phase serum progesterone concentration >30 nmol/L (a concentration consistent with ovulation) in a dose-related manner in cycle 2 (P=0.002). Treatment did not produce vasomotor symptoms. Conclusions NK1,3 receptor antagonism with elinzanetant dose-dependently suppressed the reproductive axis in healthy women, with the 120 mg dose lowering estradiol to potentially ideal levels for UF and EM. As such, elinzanetant may represent a novel therapy to manipulate reproductive hormone levels in women with hormone driven disorders.


2011 ◽  
Vol 165 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Carina Ankarberg-Lindgren ◽  
Otto Westphal ◽  
Jovanna Dahlgren

ObjectiveTo characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS).DesignIn this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population.MethodsHormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer.ResultsBefore puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E2) concentrations started to increase during puberty and inhibin B and anti-Müllerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P<0.01), FSH (7.1 vs 2.5 U/l, P<0.001), testosterone (18.7 vs 15.6 nmol/l, P<0.01) and E2 (66 vs 46 pmol/l, P<0.001) levels and lower AMH (33 vs 65 pmol/l, P<0.01) and inhibin B (median 108 vs 187 pg/ml, P<0.01) levels than the reference population.ConclusionsIn NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luigi MAIONE ◽  
Sylvie SALENAVE ◽  
Severine TRABADO ◽  
Philippe Chanson ◽  
Ursula B Kaiser ◽  
...  

Abstract Context. Hypogonadotropic hypogonadism (HH) is a clinical condition defined by subnormal serum testosterone levels with low serum gonadotropins, which leads to infertility and reduced testicular function in men. HH may be prenatal or congenital (CHH) or acquired (AHH), the latter most commonly related to injury at the hypothalamic/pituitary level. Since diverse medical specialists usually deal with these two disorders, a direct comparison of clinical characteristics and reproductive hormone levels in patients with CHH and AHH has never been performed in a large series. Patients and methods. 201 men with CHH (Kallmann syndrome 52%; normosmic CHH 48%) and 479 men with AHH were included. Causes for AHH included pituitary tumors (74.6%), other intracranial tumors (12.7%; craniopharyngioma 9.1%), infiltrative diseases (3.5%), and other causes (9.2%). We excluded patients with idiopathic late-onset or metabolically-related AHH from this analysis. Testicular volume (TV), serum gonadotropins, total and bioavailable testosterone (TT and BT), estradiol (E2) and testicular peptides inhibin B (IB), AMH and INSL3 were measured at a single center in the absence of any hormone replacement. Results. TV was greater in patients with AHH (16.2±6.3 mL) than in those with CHH (3.4±2.7 mL; p&lt;0.0001). Testicular hypotrophy (mean TV&lt;12 mL) was found in 30% of patients with AHH and in 97% of those with CHH (p&lt;0.0001). When adjusted for age and BMI, men with AHH still had a larger mean TV than those with CHH (p&lt;0.0001). Cryptorchidism was more frequent in patients with CHH than in those with AHH (20.4 vs 0.2%, p&lt;0.0001). Micropenis was found exclusively in patients with CHH. TT levels were higher in patients with AHH (1.4±0.9 ng/mL) than in those with CHH (0.4±0.3 mL, p&lt;0.0001). LH, FSH, BT and E2 were higher in patients with AHH than in those with CHH (p&lt;0.0001 for all parameters), as were IB and INSL3 levels (126±87 vs 59±55 pg/mL, and 566±372 vs 60±40 pg/mL, respectively, p&lt;0.001). In contrast, serum AMH and SHBG levels were lower in patients with AHH than in those with CHH (246±234 vs 46±38 pmol/L, and 35±22 vs 26±21 nmol/L, respectively, p&lt;0.0001). Comparing hormone characteristics across different AHH subgroups, patients with craniopharyngioma (n=44) had lower TV (7.7±5.3 mL) and lower TT, BT, E2, IB and INSL3 levels than those with AHH caused by any other etiology (p&lt;0.05 for all parameters). Conclusions. Our data demonstrate distinct profiles of clinical presentation and reproductive hormones between CHH and AHH. Clinical and hormonal impairment is more severe in patients with CHH than in those with AHH. Preservation of the gonadotrope/testicular axis activity during the fetal, neonatal and pubertal periods in patients with AHH likely accounts for these differences. Among AHH etiologies, patients with craniopharyngioma have the most severe impairment, likely as a result of the intrinsic severity of these tumors, the age at onset, and/or the aggressiveness of the available therapeutic procedures.


2005 ◽  
Vol 17 (5) ◽  
pp. 507 ◽  
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of β-endorphin (β-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus–pituitary–ovary (HPO) axis of the SAMP8 strain as hypergonadotropic–hypogonad. The levels of β-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in β-EP and SP concentrations in the hypothalamus.


2009 ◽  
Vol 21 (4) ◽  
pp. 624
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of �-endorphin (�-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus.pituitary.ovary (HPO) axis of the SAMP8 strain as hypergonadotropic.hypogonad. The levels of �-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in �-EP and SP concentrations in the hypothalamus.


Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1255
Author(s):  
Cheol Lee ◽  
SeongNam Park ◽  
ByoungRyun Kim ◽  
Hyeonbin Yim ◽  
Myeongjong Lee ◽  
...  

Background and Objectives: Female reproductive hormones may affect core body temperature. This study aimed to investigate the effects of female reproductive hormones on inadvertent intraoperative hypothermia in patients who underwent laparoscopic gynecologic surgery under general anesthesia. Materials and Methods: This retrospective study included 660 menstruating and menopausal female patients aged 19–65 years. The patients were divided into two groups according to the occurrence of inadvertent intraoperative hypothermia: non-hypothermia group (N = 472) and hypothermia group (N = 188). After propensity score matching, 312 patients (N = 156 in each group) were analyzed to investigate the association between intraoperative hypothermia and female reproductive hormones. As potential predictors of inadvertent hypothermia, the levels of female reproductive hormones were analyzed using binary logistic regression. Results: The association of estradiol (r = −0.218, p = 0.000) and progesterone (r = −0.235, p = 0.000) levels with inadvertent intraoperative hypothermia was significant but weakly negative before matching; however, it was significant and moderately negative after matching (r = −0.326, p = 0.000 and r = −0.485, p = 0.000, respectively). In a binary logistic analysis, the odds ratio for estradiol was 0.995 (p = 0.014, 0.993 < 95% confidence interval [CI] < 0.998) before matching and 0.993 (p = 0.000, 0.862 < 95% CI < 0.930) after matching, and that for progesterone was 0.895 (p = 0.000, 0.862 < 95% CI < 0.930) before matching and 0.833 (p = 0.014, 0.990 < 95% CI < 0.996) after matching. Conclusions: Estradiol and progesterone levels were associated with inadvertent intraoperative hypothermia. However, the odds ratio for female reproductive hormone levels was close to 1. Therefore, female reproductive hormones may not be a risk factor for hypothermia during gynecologic surgery under general anesthesia. However, a small sample size in this study limits the generalizability of the results.


2020 ◽  
Author(s):  
Pahriya Ashrap ◽  
John D. Meeker ◽  
Brisa N. Sánchez ◽  
Niladri Basu ◽  
Marcela Tamayo-Ortiz ◽  
...  

Abstract Background: Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.Methods: Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone levels [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8–14, 10-18 years). We used linear regression to independently examine urinary metal levels in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.Results: In utero and prepubertal concentrations of some urinary metals were associated with increased levels of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.Conclusion: These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.


2020 ◽  
Vol 26 (6) ◽  
pp. 682-690
Author(s):  
Ahmed Al Menabbawy ◽  
Ehab El Refaee ◽  
Mohamed A. R. Soliman ◽  
Mohamed A. Elborady ◽  
Mohamed A. Katri ◽  
...  

OBJECTIVECerebral ventriculitis remains one of the most challenging neurosurgical conditions, with poor outcome and a long course of treatment and duration of hospital stay. Despite the current conventional management plans, i.e., using antibiotics in addition to CSF drainage, the outcome remains unsatisfactory in some cases, with no definitive therapeutic guidelines. This study aims to compare the outcome of ventricular irrigation/lavage (endoscopic irrigation or the double-drain technique) to conventional currently accepted therapy using just drainage and antibiotics.METHODSThe authors conducted a prospective controlled study in 33 patients with cerebral ventriculitis in which most of the cases were complications of CSF shunt operations. Patients were divided into two groups. Removal of the ventricular catheter whenever present was performed in both groups. The first group was managed by ventricular lavage/irrigation, while the other group was managed using conventional therapy by inserting an external ventricular drain. Both systemic and intraventricular antibiotics were used in both groups. The outcomes were compared regarding mortality rate, modified Rankin Scale (mRS) score, and duration of hospital stay.RESULTSThe mean age of the study population was 5.98 ± 7.02 years. The mean follow-up duration was 7.6 ± 3.2 months in the conventional group and 5.7 ± 3.4 months in the lavage group. The mortality rate was 25% (4/16) in the lavage group and 52.9% (9/17) in the nonlavage group (p = 0.1). The mRS score was less than 3 (good outcome) in 68.8% (11/16) of the lavage group cases and in 23.5% (4/17) of the conventional group (p < 0.05). The mean hospital stay duration was 20.5 ± 14.2 days in the lavage group, whereas it was 39.7 ± 16.9 days in the conventional group (p < 0.05).CONCLUSIONSVentricular lavage or irrigation together with antibiotics is useful in the management of cerebral ventriculitis and associated with a better outcome and shorter hospital stay duration compared to current conventional lines of treatment.


Children ◽  
2020 ◽  
Vol 7 (9) ◽  
pp. 140
Author(s):  
So Rae Lee ◽  
Su Min Kim ◽  
Min Young Oh ◽  
Jae Min Lee

This study was conducted to investigate the safety and efficacy of olanzapine for high and moderate emetogenic chemotherapy in children and young adults. We retrospectively reviewed the records of pediatric patients (n = 13) with cancer who had been administered olanzapine as an anti-emetic drug (AED) during a high and moderate emetogenic chemotherapy block from January 2018 to March 2020. Patients were administered other prophylactic AEDs according to practice guidelines. The mean age of the patients was 14.1 ± 5.5 years. The total number of chemotherapy cycles was 41. Twenty-one (51.2%) chemotherapy blocks were high emetogenic chemotherapy and 20 (48.8%) blocks were moderate emetogenic chemotherapy. Olanzapine was used for prophylaxis in 20 (48.8%) blocks of chemotherapy and rescue in 21 (51.2%). Of the 41 cycles, a complete response to olanzapine was achieved in 31 (75.6%), partial response in 6 (14.6%), and no response in 4 (9.8%). The mean dose was 0.07 ± 0.04 mg/kg/dose and 2.50 ± 1.37 mg/m2/dose. Adverse effects included somnolence, hyperglycemia, fatigue, and disturbed sleep. Our findings indicate that olanzapine was effective and safe for treating chemotherapy-induced nausea and vomiting in children. A prospective controlled study is needed to confirm these findings.


2014 ◽  
Vol 86 (4) ◽  
pp. 284 ◽  
Author(s):  
Maria Angela Cerruto ◽  
Fabio Vianello ◽  
Carolina D’Elia ◽  
Walter Artibani ◽  
Giovanni Novella

Background: The ideal bioptic strategy for CaP detection is still to be completely defined. The aim of our study is to compare transperineal (TP) and transrectal (TR) approaches, in a 14-core initial prostate biopsy for CaP detection. Material and methods: A prospective controlled study was conducted enrolling 108 consecutive patients with a PSA level greater than 4 ng/mL and/or an abnormal DRE. TR versus TP 14-core initial prostatic biopsies were performed on 54 and 54 patients, respectively, with a randomisation ratio of 1:1. Results: The cancer detection rates were 46.29 (25 out of 54 patients), and 44.44% (24 out of 54 patients), respectively, using the TR or the TP approach (p = 0.846). The overall cancer core rate was significantly higher when the TP approach was used: 21.43% (162 out of 756 cores) and 16.79% (127 out of 756 cores), with the TP and the TR approach, respectively (p = 0.022). The cores were significantly longer performing TP approach: at the site “1” (14.92 versus 12.97 mm, p = 0.02); at “5” (15.53 versus 13.69 mm, p = 0.037); at “7” (15.06 versus 12.86 mm, p = 0.001); at “9” (14.92 versus 13.38 mm, p = 0.038); at “11” (16.32 versus 12.31 mm, p = 0.0001); at “12” (15.14 versus 12.19 mm, p = 0.0001); at “13” (17.49 versus 13.98 mm, p = 0.0001); at “14” (16.77 versus 13.36 mm, p = 0.0001). As to the biopsy related pain, the mean pain level perceived by patients during the TR approach was 1.56 ± 1.73 versus 1.42 ± 1.37 registered during TP approach (p = 0.591). Conclusions: No significant differences were found in cancer detection rate, cancer core rate between TP and TR approaches for prostatic biopsy. Even in terms of complication rate or pain level, it cannot be concluded that one procedure is superior to the other one. Apparently, strictly following our protocol, TP approach seems to offer a better sampling at the level of the apex and the TZ, however without adding any significant advantage in terms of overall cancer detection rate.


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