scholarly journals Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women

2021 ◽  
Author(s):  
Steve Pawsey ◽  
Edouard Gregory Mills ◽  
Elizabeth Ballantyne ◽  
Kirsteen Donaldson ◽  
Mary Kerr ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Hormone Secretion ◽  
Reproductive Hormones ◽  
Controlled Study ◽  
Vasomotor Symptoms ◽  
Reproductive Hormone ◽  
Novel Therapy ◽  
Serum Progesterone ◽  
Hormone Levels ◽  
Healthy Women

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.

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 ◽  
...  
Keyword(s):  
Pubertal Development ◽  
Hormonal Contraception ◽  
Reproductive Hormones ◽  
Inhibin B ◽  
Controlled Study ◽  
Age At Menarche ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
The Mean ◽  
Prospective Controlled Study

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.

Patterns of reproductive hormone secretion in hibernating Turkish hamsters

1987 ◽  
Vol 253 (2) ◽  
pp. R329-R336 ◽  
Author(s):  
J. M. Darrow ◽  
L. Yogev ◽  
B. D. Goldman
Keyword(s):  
Temporal Pattern ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Winter Season ◽  
Reproductive Hormones ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Short Day ◽  
Testicular Recrudescence ◽  
Testicular Size

Changes in gonadal state and in circulating reproductive hormones [follicle-stimulating hormone (FSH), prolactin (PRL), and testosterone] were studied for 30 wk in male Turkish hamsters (Mesocricetus brandti) induced to hibernate by exposure to a short-day, cold environment [10:14-h light-dark (LD) cycle, 6 +/- 1 degree C]. Similar measures were compared in hamsters maintained under short-day warm conditions (10:14-h LD, 21 +/- 2 degrees C). A decrease in testicular size and in hormone levels was observed after 9-12 wk of short-day exposure in all animals. After 24 wk, hormone levels rose again, accompanied by testicular recrudescence, in short-day warm hamsters and in hamsters that failed to hibernate in the cold. For animals that hibernated the temporal pattern of endocrine and gonadal changes differed only slightly in comparison. Testicular recrudescence of hibernators lagged approximately 3 wk behind that of short-day warm hamsters. Hormone levels were generally lower in hibernators sampled during bouts of torpor than during bouts of spontaneous arousal from torpor. A marked elevation of serum FSH was observed in aroused hibernators well before the end of the hibernation season (at 21 wk of short-day exposure). Mean testosterone and PRL values had increased by wk 27, after hibernation was terminated in the majority of animals. These results indicate that testosterone may not be essential for the termination of the hibernation season. The data also suggest that an endogenous timing mechanism, resistant to the decreased body temperature experienced during torpor, may function to trigger a resurgence of the neuroendocrine-gonadal axis at the end of the winter season.

scholarly journals Conception Rate and Reproductive Hormone Secretion in Holstein Cows Immunized against Inhibin and Subjected to the Ovsynch Protocol

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 313 ◽  
Author(s):  
Rihong Guo ◽  
Fang Chen ◽  
Cheng Mei ◽  
Zicun Dai ◽  
Leyan Yan ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Reproductive Performance ◽  
Luteal Phase ◽  
Low Dose ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Plasma Concentrations ◽  
High Dose ◽  
Reproductive Hormone ◽  
Conception Rates

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

scholarly journals Acute Effects of Glucagon on Reproductive Hormone Secretion in Healthy Men

2020 ◽  
Vol 105 (6) ◽  
pp. 1899-1905
Author(s):  
Chioma Izzi-Engbeaya ◽  
Sophie Jones ◽  
Yoshibye Crustna ◽  
Pratibha C Machenahalli ◽  
Deborah Papadopoulou ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Reproductive Hormones ◽  
Metabolic Effects ◽  
Acute Administration ◽  
Reproductive Hormone ◽  
Glucagon Receptor ◽  
Healthy Men ◽  
Testosterone Levels ◽  
Reproductive Axis ◽  
Lh Pulsatility

Abstract Context Glucagon increases energy expenditure; consequently, glucagon receptor agonists are in development for the treatment of obesity. Obesity negatively affects the reproductive axis, and hypogonadism itself can exacerbate weight gain. Therefore, knowledge of the effects of glucagon receptor agonism on reproductive hormones is important for developing therapeutics for obesity; but reports in the literature about the effects of glucagon receptor agonism on the reproductive axis are conflicting. Objective The objective of this work is to investigate the effect of glucagon administration on reproductive hormone secretion in healthy young men. Design A single-blinded, randomized, placebo-controlled crossover study was conducted. Setting The setting of this study was the Clinical Research Facility, Imperial College Healthcare NHS Trust. Participants Eighteen healthy eugonadal men (mean ± SEM: age 25.1 ± 1.0 years; body mass index 22.5 ± 0.4 kg/m2; testosterone 21.2 ± 1.2 nmol/L) participated in this study. Intervention An 8-hour intravenous infusion of 2 pmol/kg/min glucagon or rate-matched vehicle infusion was administered. Main Outcome Measures Luteinizing hormone (LH) pulsatility; LH, follicle-stimulating hormone (FSH), and testosterone levels were measured. Results Although glucagon administration induced metabolic effects (insulin area under the curve: vehicle 1065 ± 292 min.µU/mL vs glucagon 2098 ± 358 min.µU/mL, P < .001), it did not affect LH pulsatility (number of LH pulses/500 min: vehicle 4.7 ± 0.4, glucagon 4.2 ± 0.4, P = .22). Additionally, there were no significant differences in circulating LH, FSH, or testosterone levels during glucagon administration compared with vehicle administration. Conclusions Acute administration of a metabolically active dose of glucagon does not alter reproductive hormone secretion in healthy men. These data are important for the continued development of glucagon-based treatments for obesity.

scholarly journals OR11-05 Clinical Characteristics and Reproductive Hormone Levels in 201 Men With Congenital and 479 Men With Acquired Hypogonadotropic Hypogonadism: A Single-Center Comparative Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luigi MAIONE ◽  
Sylvie SALENAVE ◽  
Severine TRABADO ◽  
Philippe Chanson ◽  
Ursula B Kaiser ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Late Onset ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Age At Onset ◽  
Pituitary Tumors ◽  
Reproductive Hormones ◽  
Reproductive Hormone ◽  
Single Center ◽  
Hormone Levels

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<0.0001). Testicular hypotrophy (mean TV<12 mL) was found in 30% of patients with AHH and in 97% of those with CHH (p<0.0001). When adjusted for age and BMI, men with AHH still had a larger mean TV than those with CHH (p<0.0001). Cryptorchidism was more frequent in patients with CHH than in those with AHH (20.4 vs 0.2%, p<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<0.0001). LH, FSH, BT and E2 were higher in patients with AHH than in those with CHH (p<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<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<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<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.

Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

2005 ◽  
Vol 17 (5) ◽  
pp. 507 ◽  
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang
Keyword(s):  
Substance P ◽  
Luteinising Hormone ◽  
Reproductive Hormones ◽  
Oestrous Cycle ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Age Related ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Age Related Changes

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.

Erratum to: Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

2009 ◽  
Vol 21 (4) ◽  
pp. 624
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang
Keyword(s):  
Substance P ◽  
Luteinising Hormone ◽  
Reproductive Hormones ◽  
Oestrous Cycle ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Age Related ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Age Related Changes

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.

scholarly journals Effects of Female Reproductive Hormone Levels on Inadvertent Intraoperative Hypothermia during Laparoscopic Gynecologic Surgery: A Retrospective Study

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1255
Author(s):  
Cheol Lee ◽  
SeongNam Park ◽  
ByoungRyun Kim ◽  
Hyeonbin Yim ◽  
Myeongjong Lee ◽  
...  
Keyword(s):  
Retrospective Study ◽  
General Anesthesia ◽  
Odds Ratio ◽  
Reproductive Hormones ◽  
Gynecologic Surgery ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Intraoperative Hypothermia ◽  
Hypothermia Group ◽  
Laparoscopic Gynecologic Surgery

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.

scholarly journals In Utero and Peripubertal Metals Exposure in Relation to Reproductive Hormones and Sexual Maturation and Progression among Boys in Mexico City

2020 ◽  
Author(s):  
Pahriya Ashrap ◽  
John D. Meeker ◽  
Brisa N. Sánchez ◽  
Niladri Basu ◽  
Marcela Tamayo-Ortiz ◽  
...  
Keyword(s):  
Sexual Maturation ◽  
Pubic Hair ◽  
In Utero ◽  
Reproductive Hormones ◽  
Testicular Volume ◽  
Metal Exposure ◽  
Reproductive Hormone ◽  
Essential Metal ◽  
Hormone Levels ◽  
Metal Levels

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.

The early luteal hormonal profile in IVF patients triggered with hCG

2020 ◽  
Vol 35 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Lan N Vuong ◽  
Tuong M Ho ◽  
Toan D Pham ◽  
Vu N A Ho ◽  
Claus Yding Andersen ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Luteal Phase ◽  
Conflicts Of Interest ◽  
Progesterone Level ◽  
Reproductive Outcomes ◽  
Serum Progesterone ◽  
Hormonal Profile ◽  
Luteal Phase Support ◽  
Hormone Levels ◽  
Hcg Trigger

Abstract STUDY QUESTION What is the early luteal phase hormonal profile in patients undergoing ovarian stimulation for IVF/ICSI followed by hCG trigger and a freeze-all strategy without luteal phase support? SUMMARY ANSWER The peak concentration of progesterone occurred 4 days after oocyte pick-up (OPU + 4), with an average 35% fall from OPU + 4 to OPU + 6, and progesterone levels before and 12 h after hCG administration predicted levels during the early luteal phase. WHAT IS KNOWN ALREADY The luteal phase during IVF differs from that during normal cycles, particularly with respect to the serum progesterone level profile. This can cause asynchrony between the embryo and the endometrium, potentially resulting in implantation failure and poor reproductive outcomes. STUDY DESIGN, SIZE, DURATION This prospective study included 161 women with normal ovarian reserve receiving GnRH antagonist co-treatment during ovarian stimulation with FSH who were followed up to 6 days after OPU in a single IVF cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18–42 years undergoing IVF with ovarian stimulation using FSH were included. Ovulation was triggered with recombinant hCG 250 μg. Hormone levels were determined from blood samples taken on the day of trigger, before hCG, at 12, 24 and 36 h after hCG and at 1, 2, 3, 4, 5 and 6 days after OPU. The primary endpoint was early luteal phase serum concentrations of progesterone, LH, estradiol and hCG. MAIN RESULTS AND THE ROLE OF CHANCE One outlier with a pre-hCG serum progesterone level of 11.42 ng/mL was excluded, so all analyses included 160 subjects. Progesterone levels began to increase 1 day after OPU, peaked 4 days after OPU (114 ng/mL), then declined from OPU + 5 onwards. Peak progesterone levels were at OPU + 4, OPU + 5 or OPU + 6 in 38.8, 29.4 and 13.8% of patients, respectively. Approximately two-thirds of patients had a fall in serum progesterone from OPU + 4 to OPU + 6. Pre-hCG progesterone levels correlated significantly with those at 24 h after hCG (r2 = 0.28; P &lt; 0.001), which in turn correlated significantly with progesterone at OPU + 4 (r2 = 0.32; P &lt; 0.001). LH peaked (4.4 IU/L) 12 h after hCG trigger, persisting for 24 h but was barely elevated compared with physiological levels. Serum estradiol peaked twice: at 24 h post-trigger and at OPU + 4. Highest hCG levels (130 mIU/mL) occurred at 24 h post-injection. The best correlations between the number of follicles ≥11 mm and serum progesterone level were seen at 24 and 36 h after hCG and OPU + 1. LIMITATIONS, REASONS FOR CAUTION The influence of different profiles of serum progesterone on reproductive outcomes could not be determined because a freeze-all strategy was used in all patients. In addition, data were not available to relate serum hormone level findings with endometrial histology or endometrial receptivity analysis to clearly identify the relationship between serum hormones and the window of implantation. WIDER IMPLICATIONS OF THE FINDINGS Detailed information about early luteal phase hormone levels could be used to optimize and individualize luteal phase support to improve reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. All authors state that they have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER NCT02798146; NCT03174691.

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