High Progesterone Levels Research Articles

High serum progesterone levels on the day of embryo transfer in patients undergoing artificial frozen-thawed blastocyst transfer: Is there a ceiling effect?

To evaluate the potential ceiling effect of high serum progesterone levels on the day of embryo transfer for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer (FET) cycles. This retrospective cohort study included 595 patients who underwent artificial FET cycles. We evaluated progesterone levels and found that 40.6 ng/mL corresponded to the 90th percentile and 23.9 ng/mL corresponded to the 50th percentile. Based on these findings, we categorized progesterone levels as <20 ng/mL (n=220, 37.0%), 20-40 ng/mL (n=312, 52.4%), and ≥40 ng/mL (n=63, 10.6%). The primary outcome measures were the clinical pregnancy rate (CPR) and live birth rate (LBR). Blastocyst morphology grades, including expansion, trophectoderm, and inner cell mass grades, were significantly associated with clinical pregnancy (p<0.001 for all). Progesterone levels between 20 and 40 ng/mL were associated with higher CPR (p=0.043). In the multivariate analysis, only blastocyst expansion and inner cell mass grades were independently and significantly associated with CPR [p=0.011, odds ratio (OR)=1.6, (confidence interval) CI 95%=1.13-2.39, and p=0.007, OR=1.65, CI 95%=1.14-2.39, respectively]. The progesterone level and trophectoderm grade were not statistically significant. Regarding LBR, only blastocyst expansion grades 4 and trophectoderm grades A or B were significantly associated. Based on these data, we speculate that if serum progesterone levels exceed 40 ng/mL on the day of embryo transfer in patients undergoing artificial FET cycles, there is no need to reduce the progesterone dose.

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.

Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.

What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. The retrospective study design and the small sample size can limit the accuracy of the estimates. Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. This study did not receive funding. The authors declare that there is no conflict of interest. N/A.

Longitudinal associations of social jetlag with obesity indicators among adolescents - Shanghai adolescent cohort

ObjectiveTo explore the longitudinal association between social-jetlag (SJL) and obesity development among adolescents, sex-difference and related modifying factors in the association. MethodsBased on Shanghai-Adolescent-Cohort during 2017–2021, a total of 609 students were investigated. In grade 6, 7 and 9, the information on SJL was collected using questionnaires, and anthropometric measures were conducted. The fingernail cortisol and progesterone levels in grade 6 (using LC-MS/MS) and body composition in grade 9 (using Inbody-S10) were measured. By the latent-class-mixture-modeling, two trajectories for SJL (high-level vs. low-level) throughout 4 years were developed. The prospective associations of SJL trajectories and weight/fat gains were analyzed by sex and under different (high/moderate/low) cortisol/progesterone stratifications. ResultsIn grades 6–9, 39.00%–44.50 % of adolescents experienced at least 1 h of SJL. Compared with the low-level SJL trajectory, the high-level SJL trajectory was associated with greater differences in body-mass-index Z-scores and waist-to-height ratios across 4 years, higher levels of body-fat-percentage and fat-mass-index in grade 9 (P-values<0.05), and such associations were stronger among girls and under moderate-to-high (vs. low) baseline cortisol and progesterone levels. However, no significant associations among boys were observed. ConclusionsHigh-level SJL in adolescents may be associated with the development of obesity, especially among adolescent girls and under relatively high baseline cortisol and progesterone levels.

O-011 Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Efficacy of natural progesterone

Abstract Study question Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Summary answer Inhibition of the LH surge by progesterone during the luteal phase of duostim protocols in POR appears to be effective, safe and makes GnRH-antagonists unnecessary. What is known already High levels of progesterone have long been shown to reversibly block the LH surge associated with increased estradiol levels, by reducing GnRH’s pulsatility from the hypothalamus. This inhibition is the basis of progestin-only contraceptives and has been shown to be completely reversible by discontinuing the progestin, and even seems to have a potentiating effect on the surge which occurs in the subsequent few days Study design, size, duration This is a secondary analysis of the BISTIM study, a multicentre, open-labelled randomized controlled trial, performed in 4 french IVF centers from 2018 to 2021, designed to compare Duostim protocol versus two follicular stimulations. We here present a paired-controlled study including patients randomized in the Duostim group, who underwent 2 consecutive stimulations in the same menstrual cycle, we compare the follicular phase stimulation with GnRH-antagonist versus the luteal phase stimulation with progesterone. Participants/materials, setting, methods The BISTIM study recruited poor ovarian reserve women defined with Bologna criteria who enrolled in an IVF or ICSI program, aged from 20 to 41, with BMI from 19 to 32, with no more than 2 previous IVF cycles. Women with amenorrhea, FSH &amp;gt;20 UI/L or CFA &amp;lt;1 were not included. 32 of them underwent two stimulations, consecutively. Main results and the role of chance For the same group of 32 women, stimulation parameters were similar between 1st and 2nd stimulations (stimulation duration, gonadotropin doses, number of retrieved oocytes). As expected, progesterone levels were significantly higher at D5 in the study group compared to controls (mean 34.8 ng/ml, Q1-Q3 [18.4 – 51.6])) and were still significantly higher at HCG-day (10.7 ng/ml, Q1-Q3 [2.7 – 14.3])), despite the addition of natural exogenous progesterone. LH levels were significantly lower in the progesterone group, regardless of the day of stimulation: at HCG day mean LH was 1,7 UI/L in the study group versus 6.8 UI/L in the control group, p &amp;lt; 0.001. In the Duostim group no premature LH surge/ovulation was observed, however, 2 cancellations for premature ovulation were reported with antagonist protocol in the control group of the BISTIM study. Limitations, reasons for caution This study was carried out on a limited number of subjects (n = 32), all of whom were poor responders. Wider implications of the findings This study shows the effectiveness of LH surge inhibition by progestins, which represent a less expensive and more patient-friendly treatment than traditional protocols. Further studies are needed to determine the best protocol (type and doses of progestins) to effectively inhibit the LH surge, and on larger and different cohorts. Trial registration number 2017-A00498-45

P-412 Elevated progesterone levels after hormone replacement therapy (HRT) for frozen embryo transfer (FET) does not impair IVF outcomes, a retrospective study

Abstract Study question Does high serum progesterone (P) level on the day of FET after hormone replacement therapy affect IVF outcomes? Summary answer The supraphysiological serum progesterone levels on the day of FET after HRT do not impair reproductive outcomes. What is known already A proper synchronization between embryo and the endometrium is still required by controlling the timing and the dosage of exposure to exogenous hormones. Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during FET cycles. However, based on existing research, the relationship between progesterone levels on FET day and pregnancy outcomes as well as the certain dose of progesterone ideally to achieve pregnancy and a live birth are debatable topics Study design, size, duration This is an observational, retrospective and cohort study including 7539 FET cycles that were performed under artificial endometrial preparation with HRT using exogenous estradiol and progesterone (vaginal, subcutaneous and intramuscular) between January 2017 and December 2022. Both euploid FET from autologous oocyte ICSI-PGT-A cycles (n = 1822) or FET from ICSI cycles using donated oocytes (n = 5724) were considered. Participants/materials, setting, methods Women were divided into three groups according to P4 level on the day of FET:P&amp;lt;20 ng/ml (n = 6623),P≥20-40 ng/ml (n = 770) and P &amp;gt; 40 ng/ml (n = 146).All ET were performed at the blastocyst stage.The primary outcome was live birth rate (LBR). Secondary outcomes evaluated were biochemical, clinical, and ongoing pregnancy, and miscarriage rate (MR) calculated per FET.Categorical variables were compared between groups with Fisher’s exact test. Logistic regression models adjusted (AOR) with several confounders. Main results and the role of chance There were no significant differences in baseline characteristics of the study population. The mean of P4 level was 15,66 ng/ml. Female age was P &amp;lt; 20:38.7 ±3.1, P ≥ 20-40: 39.0 ±3.0, and P &amp;gt; 40: 38.1 ±2.9 (p = 0.53) years old. The group with the highest progesterone levels always found lower biochemical pregnancy even no statistically significant [64.6% (P &amp;lt; 20) vs 63.7% (P ≥ 20-&amp;lt;40) vs 61.1% (P &amp;gt; 40); p = 0.62]; in clinical pregnancy [56.3% (P &amp;lt; 20) vs 56.8% (P ≥ 20-&amp;lt;40) vs 51.4% (P &amp;gt; 40); p = 0.5] and in ongoing [47.0% (P &amp;lt; 20) vs 47.0% (P ≥ 20-&amp;lt;40) vs 41.8% (P &amp;gt; 40); p = 0.47] pregnancy rates. The MR was also higher in the group with higher progesterone, although not significantly: 16.2% (P &amp;lt; 20) vs 15.0% (P ≥ 20-&amp;lt;40) vs 18.0% (P &amp;gt; 40) (p = 0.60). No statistically significant differences were reported for live birth rate, 41.8% (P &amp;lt; 20) vs 40.3% (P ≥ 20-&amp;lt;40) vs 34.2% (P &amp;gt; 40) (p = 0.2). The multivariate analysis showed an increased risk of miscarriage when P &amp;gt; 40ng/ml, aOR= 1.14 (0.75-1.74) (p = 0.55) whereas no such association was found with P4 ≥20-40 ng/ml, aOR=0.92 (0.74-1.15) (p = 0.46). Additionally, the probability of live birth is similar when the patient was P &amp;gt; 40 (aOR= 0.77 (0.51-1,15) (p = 0.20)) than when P ≥ 20-&amp;lt;40 (aOR=0.94 (0.79-1,11) (p = 0.47) compared with the references group. Limitations, reasons for caution The retrospective design and different female factors for IVF were included in the study leading to a possible biased population although the adjusted analysis. Different routes of progesterone administration were considered in the study. Currently, we don’t report the timing between the last P4 administration and dosage on the FET. Wider implications of the findings This information is useful for clinicians who monitor progesterone levels prior to FET to avoid reaching high levels that would undermine the chances of achieving a newborn. Trial registration number Not Applicable

Sex-steroid hormones relate to cerebellar structure and functional connectivity across adulthood.

Aging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer's, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.

Association between Salivary Hormones, Dental Caries, and Cariogenic Microorganisms during Pregnancy.

Objective: This study aimed to identify the salivary levels of six hormones (progesterone, estradiol, testosterone, cortisol, thyroxine T3, and triiodothyronine T4) in pregnant women, and to assess the association between salivary hormones, dental caries, and cariogenic microorganisms. Methods: This cross-sectional study included 181 low-income US pregnant women who were in their third trimester. Demographic details, oral hygiene practices, and medical backgrounds were obtained via questionnaires and medical records. Calibrated dentists obtained data on plaque index and caries status through comprehensive oral examinations. Unstimulated saliva was collected 2 h before eating and brushing. Salivary hormones were measured with a multiplex assay. Oral Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) were quantified via colony-forming unit (CFU) counts. A latent model was used to generate clusters of pregnant women based on salivary hormone levels, followed by post-clustering analysis. Factors associated with salivary cariogenic microorganisms were further evaluated via multiple regression analyses. Results: Estradiol, progesterone, testosterone, cortisol, T3, and T4 in saliva were detectable at rates of 92%, 97%, 77%, 99%, 71%, and 50%, respectively. Three distinct participant clusters (high, intermediate, and low) were identified based on salivary hormone levels. Intermediate-level and high-level clusters had increased numbers of decayed teeth, decayed surfaces, ICDAS scores, and salivary S. mutans and C. albicans, compared to the low-level cluster (p < 0.05). Covariate analysis demonstrated that the high-level cluster was positively associated with salivary carriage of S. mutans (CFU/mL) (p < 0.05). Participants with higher levels of progesterone, estradiol, testosterone, and cortisol were associated with a high carriage status of S. mutans in saliva (>105 CFU/mL) (p < 0.05). Conclusions: This study demonstrated the feasibility of detecting salivary hormones during pregnancy and revealed the positive association between salivary steroid hormones and cariogenic pathogens.

Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells.

Heat stress-induced biochemical alterations in ovarian follicles compromise the function of granulosa cells (GCs) and the developmental competence of oocytes. Summer heat stress can have a far-reaching negative impact on overall fertility and reproductive success. Together with the heat stress, the rise of assisted reproductive technologies (ART), potential confounding hazards of in vitro handling and the absence of systemic body support in ART makes it imperative to study the heat stress ameliorative effects of vitamin C under in vitro conditions. Using in vitro heat stress treatment of 43 °C for two hours in bovine GCs, we studied the effects of vitamin C on cell growth, oxidative stress, apoptosis and cell cycle progression together with a comprehensive metabolomics profiling. This study investigates the molecular milieu underlying the vitamin C (VC)-led alleviation of heat-related disruptions to metabolic processes in bovine GCs. The supplementation of VC ameliorated the detrimental effects of heat stress by reducing oxidative stress and apoptosis while restoring cell proliferation. Normal cell function restoration in treated GCs was demonstrated through the finding of significantly high levels of progesterone. We observed a shift in the metabolome from biosynthesis to catabolism, mostly dominated by the metabolism of amino acids (decreased tryptophan, methionine and tyrosine) and the active TCA cycle through increased Succinic acid. The Glutathione and tryptophan metabolism were important in ameliorating the inflammation and metabolism nexus under heat stress. Two significant enzymes were identified, namely tryptophan 2,3-dioxygenase (TDO2) and mitochondrial phenylalanyl-tRNA synthetase (FARS2). Furthermore, our findings provide insight into the significance of B-complex vitamins in the context of heat stress during VC supplementation. This study underscores the importance of VC supplementation in heat stress and designates multiple metabolic intervention faucets in the context of ameliorating heat stress and enhancing reproductive efficiency.

High progesterone levels on the day after HCG injection has no effect on clinical pregnancy outcomes in in vitro fertilization-embryo transfer.

This study investigates the potential impact of high progesterone (P) level on the day following human chorionic gonadotropin (HCG) injection on the clinical pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET). Retrospective analysis was conducted on 6418 cycles of IVF-ET performed at Liuzhou Maternal and Child Health Hospital between August 2020 to December 2021. Excluding cycles with progesterone levels ≥1.5ng/ml on HCG injection, a total of 781 cycles were identified according to the standard, and they were divided into five groups according to the progesterone level on the day after HCG: Group A: progesterone level < 2.5 ng/ml (n = 128); Group B: 2.5 ng/ml ≤ progesterone level < 3.5 ng/ml (n = 174); Group C: 3.5 ng/ml ≤ progesterone level < 4.5 ng/ml (n = 153); Group D: 4.5 ng/ml ≤ progesterone level < 5.5 ng/ml (n = 132); Group E progesterone level ≥5.5 ng/ml(n=194). Comparative analyses of clinical data, including general clinical data, and clinical pregnancy outcomes such as clinical pregnancy rate, miscarriage rate, and live birth rate were performed among these groups. There were significant differences in estradiol levels on HCG injection, but there were no differences in available embryo rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Binary logistic regression analysis showed that there was no significant correlation between P level on the day after HCG injection and the live birth rate. Under the condition of low P level on HCG injection, high progesterone levels on the day after HCG injection does not affect the clinical pregnancy outcomes of IVF-ET.

Evaluation of Ovarian Histomorphology and Function Following Clomiphene Citrate and Human Chorionic Gonadotropin Administration in Wistar Rats

Polycystic ovarian syndrome (PCOS), affecting 5-10% of women, is a leading cause of infertility affecting 10-15% of couples globally. Human chorionic gonadotropin (hCG) and clomiphene citrate (CC) are often utilized for the treatment of PCOS. Accordingly, this study explored the effects of CC and hCG on ovarian histomorphology and fertility parameters. Twenty adult female rats were divided into four groups as follows: Group A (control) received only feed and water; Group B received 0.7 mg/kg BW of CC twice daily for five days and was mated before sacrifice on day 19 (before litter); Group C received 0.7 mg/kg BW of CC twice daily for five days, followed by mating and allowed to litter before sacrifice; Group D received 0.7 mg/kg body weight (BW) of hCG on day one, followed by 0.7 mg/kg BW of CC twice daily for five days, and were mated before sacrifice on day 7 (before litter). Results showed that Group B rats had higher, more than other groups, Follicle-stimulating hormone (FSH), Estradiol, Testosterone and Prolactin levels when compared to the control. Similarly, rats in Group B had higher levels of Progesterone while Group D had higher levels of Luteinizing hormone (LH) when compared to the control group. Histological findings demonstrated diverse impacts on ovarian structures, ranging from congested blood vessels to haemorrhages and follicular cysts. Consequently, this study underscores the complexities of drug interactions in reproductive health and provides preliminary insights into the possible adverse effects of CC and hCG on the ovary and fertility parameters.

Edible bird's nest improves the premature ovarian failure induced by tripterygium glycosides.

Premature ovarian failure (POF) is a common disease in the field of gynecological endocrinology that seriously affects the physical and mental health of patients. Previous studies found that edible bird's nest (EBN) could improve uterine function. These suggested that EBN might also have an ameliorating effect on POF. Therefore, in this study, tripterygium glycosides (TGs) were used to induce POF in rats, and the effect of EBN on the improvement of POF was investigated. After the administration of EBN for 14 days, ovarian index and uterine index, serum hormone levels, apoptosis rate of ovarian granulosa cells, follicle-stimulating hormone receptor (FSHR) protein expression level, and the histopathological examination of the ovaries were determined. It was found that administration of medium and high EBN dose groups increased the ovarian index and granular layer thickness of rats with POF. Particularly, higher follicle-stimulating hormone levels and lower corpus luteum content were observed in the high EBN dose group. In addition, there were lower luteinizing hormone levels and fewer atretic follicles but higher progesterone levels in the medium EBN dose group. These results indicated that EBN had preventive and curative effects on POF induced by TGs. Its mechanism of action might be related to the reduction of ovarian granulosa cell apoptosis, regulation of hormones and receptors, and inhibition of follicle closure.

Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. The study was registered at Clinical Trials Gov. (NCT04108039).

Survival and hormone production of isolated mouse follicles in three-dimensional artificial scaffolds after stimulation with bpV(HOpic)

PurposeTo preserve fertility before gonadotoxic therapy, ovarian tissue can be removed, cryopreserved, and transplanted back again after treatment. An alternative is the artificial ovary, in which the ovarian follicles are extracted from the tissue, which reduces the risk of reimplantation of potentially remaining malignant cells. The PTEN inhibitor bpV(HOpic) has been shown to activate human, bovine and alpacas ovarian follicles, and it is therefore considered a promising substance for developing the artificial ovary. The purpose of this study was to examine the impact of different scaffolds and the vanadate derivative bpV(HOpic) on mice follicle survival and hormone secretion over 10 days.MethodsA comparative analysis was performed, studying the survival rates (SR) of isolated mice follicle in four different groups that differed either in the scaffold (polycaprolactone scaffold versus polyethylene terephthalate membrane) or in the medium—bpV(HOpic) versus control medium. The observation period of the follicles was 10 days. On days 2, 6, and 10, the viability and morphology of the follicles were checked using fluorescence or confocal microscopy. Furthermore, hormone levels of estrogen (pmol/L) and progesterone (nmol/L) were determined.ResultsWhen comparing the SR of follicles among the four groups, it was observed that on day 6, the study groups utilizing the polycaprolactone scaffold with bpV(HOpic) in the medium (SR: 0.48 ± 0.18; p = 0.004) or functionalized in the scaffold (SR: 0.50 ± 0.20; p = 0.003) exhibited significantly higher survival rates compared to the group using only the polyethylene terephthalate membrane (SR: 0). On day 10, a significantly higher survival rate was only noted when comparing the polycaprolactone scaffold with bpV(HOpic) in the medium to the polyethylene terephthalate membrane group (SR: 0.38 ± 0.20 versus 0; p = 0.007). Higher levels of progesterone were only significantly associated with better survival rates in the group with the polycaprolactone scaffold functionalized with bpV(HOpic) (p = 0.017).ConclusionThis study demonstrates that three-dimensional polycaprolactone scaffolds improve the survival rates of isolated mice follicles in comparison with a conventional polyethylene terephthalate membrane. The survival rates slightly improve with added bpV(HOpic). Furthermore, higher rates of progesterone were also partly associated with improved survival.

Faecal glucocorticoid analysis as indicator of stress and its effect on the reproduction hormones of the female Malayan sun bear (Helarctus malayanus) in captivity.

Faecal glucocorticoid metabolite (FGM) is frequently used as a non-invasive tool to assess adrenocortical activity in animal conservation and welfare studies. However, studies assessing the stress level and its effect on the reproductive hormones of female Malayan sun bear is lacking. This study aims to assess the level of stress of the female Malayan sun bear in captivity and its effect on the female reproductive hormones of the female Malayan sun bears in captivity in Malaysian Borneo. Through FGM analysis via the enzyme-linked immunoassay (ELISA) method, it was found that the bear living in BSBCC has the lowest level of glucocorticoid. as for the relationship between the level of stress and the female reproductive hormones, the level of estrogen which was indicated by estradiol, decreases as the level of FGM increases. In contrast, the level of progesterone increase as the level of FGM increases. It can be concluded that the level of stress in captivity could affect the level of estrogen and progesterone and a high level of progesterone does not always indicate a good reproductive function in female mammals.

The Relationship between the Prevalence of Cesarean Sections and Progesterone (Duphaston) Usage during Pregnancy

Background: Progesterone plays a crucial part in ovulation, implantation, and pregnancy, among other reproductive processes.This is related to progesterone's role in controlling cyclical changes in decidualization and proliferation, which regulate uterine function during the menstrual cycle. Progesterone is necessary for the development of decidual tissues. In the event of fertilization, high levels of progesterone in the blood are crucial for maintaining pregnancy by promoting uterine growth and inhibiting the effects of factors that cause myometrial contraction. During a cesarean section, the fetus is delivered via a surgical incision made in the woman's abdomen (laparotomy) and in her uterus (hysterotomy). The likelihood of experiencing health issues following a cesarean birth is somewhat increased due to the high number of caesarean sections performed globally in comparison to spontaneous births. Method: 65 pregnant women participated in this cross-sectional study, which ran from October 1, 2022, to March 20, 2023, in the gynecological department of Salah Al Deen General Hospital in the Salah al Deen governorate and in Diyala. Result: As in result of questioners in pregnancies take the progesterone as stabilizer About 75.4% of participants were delivered by cesarean section and only 24.6% were delivered by normal vaginal delivery . Conclusion: The regular use of progestagens for the treatment of impending miscarriage may have contributed to the increased rate of cesarean sections among the participants.

Predictive Role of Progesterone Levels for IVF Outcome in Different Phases of Controlled Ovarian Stimulation for Patients With and Without Endometriosis: Expert View.

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis.

Knee Laxities Changes with Sex-steroids throughout the Menstrual Cycle Phases in Athlete and Non-athlete Females.

Objective: Our study investigated changes of knee laxities in athletes and non-athletes females and relationship between knee laxity and sex-steroid at menstrual cycle phases. Methods: Forty six healthy females, twenty four athletes and twenty two non-athletes not on hormone contraceptive pills, had no previous knee injuries and with regular menstrual cycles for 3 consecutive months, participated in the study. Medial and lateral knee laxities were determined by varus-valgus tests at follicular, ovulatory and luteal phases. Serum level of relaxin, estrogen, progesterone and testosterone were determined by ELISA and radioimmunoassay. Results: Knee laxities in athletes and non-athletes at 0° and 20° flexion were the highest in luteal phase with non-athletes possess greater laxity than athletes. Positive correlation between progesterone and relaxin levels with knee laxities were observed. Meanwhile, the levels of both hormones were highest in the luteal phase. Conclusion: Increased medial and lateral knee laxities in athletes and non-athletes associated with high serum progesterone and relaxin levels in luteal phase may contribute toward increased risk of non-contact knee injury. However, lower knee laxity in athletes than non-athletes suggest that exercise could be a protective factor.

Features of gynecological status and concomitant morbidity in menopausal women with resistant rheumatoid arthritis and obesity

Oftentimes, women with RA experience remission during pregnancy. The beneficial effect of pregnancy on the RA course is associated with a specific hormonal status, including high levels of estriol and progesterone that have known anti-inflammatory effects. After childbirth, decreased endogenous production of steroids can trigger the onset or exacerbation of RA.Objective. Studying of the characteristics of the gynecological status and concomitant extragenital diseases in postmenopausal women with rheumatoid arthritis (RA) depending on the presence of obesity.Materials and methods. 394 postmenopausal women with RA (diagnosed according to ACR/EULAR 2010 criteria) were included. By decision of the medical commission, all patients were approved for therapy with genetically engineered biological drugs and/or JAK kinase inhibitors. Before inclusion in the study, all patients had a detailed medical history, an allergic history, registered comorbidities, and a physical and laboratory-instrumental examination. Depending on the BMI values, the study participants were divided into groups. Group A included 103 obese patients of any severity (BMI ≥ 30 kg/m2). Group B included 291 women with BMI &lt;30 kg/m2. Patients with an inflammatory process were found to have groups of inflammation by age and duration of RA (p &gt; 0.05).Results. In patients of group A, more often than in patients of group B, comorbidities were detected: hypertension (p &lt; 0.0001), coronary heart disease (p = 0.03), history of “vascular accidents” (p = 0.0009), especially acute cerebrovascular accident (p = 0.004), type 2 diabetes mellitus (p = 0.0005), which manifest themselves over the age of 45, that is, during the perimenopause. When correcting the gynecological history data, he draws attention to the fact that group A patients are more likely to operate surgically and on the pelvic organs: more had the uterus removed (p = 0.002) or ovarian resection was performed (p &lt; 0.0001), and the frequency of surgical menopause in group A was higher than in group B (p = 0.0009). The debut of RA on average chronologically coincided with the onset of menopause (p = 0.01). At the same time, in the average age of the onset of menopause, it is rare (p &gt; 0.05). The number of women who had a history of pregnancy, childbirth, miscarriages and abortions in the groups were repeated (p &gt; 0.05). But in group A, the average number of pregnancies (p = 0.003) and abortions (p = 0.004) per woman was higher than in group B.Conclusion. The results of the study revealed the identification of clinical manifestations of inflammation and the severity of rheumatoid arthritis, depending on the presence of concomitant obesity in postmenopausal women, as well as a rarer occurrence of osteoporosis in women with RA and concomitant obesity.

FOXL2 and NR5A1 induce human fibroblasts into steroidogenic ovarian granulosa-like cells.

Human granulosa cells in different stages are essential for maintaining normal ovarian function, and granulosa cell defect is the main cause of ovarian dysfunction. To address this problem, it is necessary to induce functional granulosa cells at different stages in vitro. In this study, we established a reprogramming method to induce early- and late-stage granulosa cells with different steroidogenic abilities. We used an AMH-fluorescence-reporter system to screen candidate factors for cellular reprogramming and generated human induced granulosa-like cells (hiGC) by overexpressing FOXL2 and NR5A1. AMH-EGFP+ hiGC resembled human cumulus cells in transcriptome profiling and secreted high levels of oestrogen and progesterone, similar to late-stage granulosa cells at antral or preovulatory stage. Moreover, we identified CD55 as a cell surface marker that can be used to isolate early-stage granulosa cells. CD55+ AMH-EGFP- hiGC secreted high levels of oestrogen but low levels of progesterone, and their transcriptome profiles were more similar to early-stage granulosa cells. More importantly, CD55+ hiGC transplantation alleviated polycystic ovary syndrome (PCOS) in a mouse model. Therefore, hiGC provides a cellular model to study the developmental program of human granulosa cells and has potential to treat PCOS.