High Progesterone Levels Research Articles

Placental transfusion: may the "force" be with the baby.

Placental transfusion results in a significant decrease in the risk of death for extremely preterm infants. With immediate cord clamping (ICC), these infants can leave up to one-half of their normal circulating in utero blood volume in the placenta. Extremely preterm infants are at highest risk of harm from ICC yet are currently the most likely to receive ICC. Receiving a placenta transfusion provides infants with life-saving components and enhanced perfusion. We present some lesser-known but important effects of placental transfusion. New research reveals that enhanced vascular perfusion causes an organ's endothelial cells to release angiocrine responses to guide essential functions. High progesterone levels and pulmonary artery pressure in the first few hours of life assist with neonatal adaptation. We propose that lack of essential blood volume may be a major factor contributing to inflammation, morbidities, and mortality that preterm infants frequently encounter.

Binding of microRNA-135a (miR-135a) to homeobox protein A10 (HOXA10) mRNA in a high-progesterone environment modulates the embryonic implantation factors beta3-integrin (ITGβ3) and empty spiracles homeobox-2 (EMX2).

BackgroundPatients with elevated circulating progesterone concentrations on the day of the human chorionic gonadotropin (hCG) trigger had relatively low implantation rates during assisted reproductive treatments. In this study, we assess the hypothesis that different concentrations of progesterone regulate the expression of homeobox protein A10 (HOXA10) and its downstream genes through miRNA-135a.MethodsMicroRNA-135a (miR-135a), HOXA10, beta3-integrin (ITGβ3), and empty spiracles homeobox-2 (EMX2) expression levels in endometrial tissues from patients with elevated progesterone were measured. To determine the threshold of progesterone level which can impair implantation, Ishikawa cells were used to determine the expression of the aforementioned 4 genes after exposure to 5 graded concentrations of progesterone. The dual-luciferase reporter assay was used to verify whether miR-135a regulated the expression of HOXA10. Furthermore, the effects of HOXA10 on the expression of key endometrial receptivity genes ITGβ3 and EMX2 were confirmed.ResultsHigh progesterone levels promoted miR-135a expression in vivo, and miR-135a bound to the 3'-untranslated region (3'-UTR) of HOXA10 mRNA to inhibit HOXA10 expression. Reduction of HOXA10 promoted EMX2 expression and inhibited ITG-3 production. Progesterone promoted the expression of HOXA10 in vitro at low concentrations. However, when the concentration was greater than 10−7 ng/mL, progesterone inhibited HOXA10 by promoting miR-135a expression, thereby altering the expression of related genes and affecting endometrial receptivity.ConclusionsIn vitro, the trend in miR-135a expression (which first decreased and then increased) was in direct contrast to that of HOXA10 expression (which first increased and then decreased) as progesterone levels increased. The key factors regulating endometrial receptivity included ITGβ3 and EMX2, which were confirmed to be regulated by HOXA10. High progesterone levels affected miR-135a expression, and miR-135a inhibited HOXA10 expression, thereby affecting endometrial receptivity.

The value of serum progesterone level on day of human chorionic gonadotrophin administration / metaphase II oocyte ratio in predicting IVF/ICSI outcome in patients with normal ovarian reserve

BackgroundThe clinical implication of the increased serum progesterone level on the day of HCG administration in assisted reproduction treatment (ART) is still controversial. The current study aimed to compare the predictive value of serum progesterone on day of HCG administration / metaphase II oocyte (P/MII) ratio on IVF/ ICSI outcome to serum progesterone (P) level alone and the ratio of serum progesterone/estradiol level (P/E2) ratio in prediction of pregnancy rates after ART.Material & methodsTwo hundred patients admitted to the IVF/ICSI program at Minia IVF center in Egypt in the period from October 2016 to May 2018 were included in this study. Serum Progesterone (P) and Estradiol (E2) levels were estimated on the day of HCG administration. The ratio between serum P and the number of MII oocytes (P/MII ratio) was calculated and the predictive values of the three parameters (P, P/E2 ratio and P/MII ratio) in prediction of cycle outcomes were measured.ResultsP/ MII oocyte ratio was significantly lower in patients who attained clinical pregnancy (n = 97) as compared with those who couldn’t whilst there was no significant difference in P and P/E2 ratio between the two groups. Using a cut off value of 0.125, the sensitivity and specificity of progesterone/ MII ratio in prediction of no pregnancy in IVF/ICSI were 75.7 and 77.1% respectively with the area under The Receiver operating curve (ROC-AUC) = 0.808. The respective values of the ROC-AUC for the P and P/E2 ratio were 0.651 and 0.712 with sensitivity and specificity of 71.2 and 73.5%for P level and of 72.5 and 75.3% for P/E2 ratio. Implantation or clinical pregnancy rates were significantly different between patients with high and low P/MII ratio irrespective of day of embryo transfer (day 3 or 5).ConclusionsIn patients with normal ovarian response, serum progesterone on day of HCG / MII oocyte ratio can be a useful predictor of pregnancy outcomes and in deciding on freezing of all embryos for later transfer instead of high progesterone level alone.

Гормональна функція жовтого тіла, трофобласта і плаценти у жінок, які завагітніли двійнями після лікування безплідності

Гормональна функція жовтого тіла, трофобласта і плаценти у жінок, які завагітніли двійнями після лікування безплідності

Clinical characteristics of 21 infertile women with non-classic 21-hydroxylase deficiency

Objective: To investigate the clinical features of infertile women with non-classic 21-hydroxylase deficiency (21-OHD). Methods: The study enrolled 21 infertile women with non-classic 21-OHD in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2009 to December 2018. The clinical presentation, endocrine hormone, glucolipid metabolism and treatment outcome were retrospectively analyzed. The diagnosis of non-classic 21-OHD was comprehensively based on clinical and hormonal characteristics. Results: Among 21 cases, the age was (29.9±2.9) years, the mean age at menarche was (13.6±2.0) years, body mass index was (22.1±2.9) kg/m2, and 38% (8/21) had oligomenorrhea. Hirsutism was diagnosed in 3 cases (14%, 3/21). Clitoromegaly was seen in 14% (3/21) and polycystic ovarian morphology was found in 33% (7/21) of the patients. The mean serum level of basal progesterone was (11.3±21.0) nmol/L, with 48% (10/21) having high basal progesterone level; after therapy by glucocorticoid, the level of progesterone was (1.9±2.0) nmol/L. Serum 17-hydroxyprogesterone concentration was (66.4±123.6) nmol/L; after therapy by glucocorticoid, it was (2.4±1.8) nmol/L. In the study increased testosterone, androstenedione and dehydroepiandrosterone sulfate were present in 62% (13/21), 52% (11/21) and 43% (9/21), respectively; and 52% (11/21) of patients manifested androgen excess and basal progesterone elevation; androgen levels decreased after therapy by glucocorticoid. The pregnancy rate was 76% (16/21). Out of 19 pregnancies, 6/19 ended in spontaneous miscarriages. Conclusions: Infertile women with non-classic 21-OHD are characterized by hyperandrogenism and basal progesterone elevation, whereas gonad axis disorder is not apparent. After no response to conventional therapy, adult infertile women with non-classic 21-OHD could achieve a desirable pregnancy outcome with proper treatment of glucocorticoid.

Relationship About KI67 and Chemotherapy Regimens About Progression Free Survival in Triple Negative Breast Cancer

Objective: To determine the experience in a public institution (Hospital General de México) the relationship of KI67% and chemotherapy regimens about the progression free survival. Design: It is a retrospective study in which a total of 64 patients with a 36-month follow-up were evaluated, evaluating the percentage of KI67 and the chemotherapy regimens, which were AC+TXL vs CBP/TXL+AC. Results: A progression-free survival of 11.9 months was demonstrated in the patients who started with the CBP / TXL-based chemotherapy regimen and sequentially AC versus the 9.7 months achieved with the conventional ACX4 scheme and later add Carboplatin and Paclitaxel, and a Overall in both arms of 10.8 months, the patients who demonstrated the presence of a higher KI67 demonstrated increased progression-free survival compared to those with a low KI67, and with an unexpected surrogate that despite being few patients, those who showed higher levels of Progesterone had a lower survival compared to percentages of 5% or negative. Conclusions: Despite the fact that the first-line scheme for triple negative breast cancer was sequential and that the sample was only 64 patients, it was shown that adding carboplatin in the first line together with Paclitaxel in patients with high KI67 and without or with a minimal percentage of progresterone receptors increases Progression Free Survival.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Adverse effects of maternal rheumatoid arthritis during pregnancy on children.

Successful live birth in a Chinese woman with P450 oxidoreductase deficiency through frozen-thawed embryo transfer: a case report with review of the literature

BackgroundCongenital adrenal hyperplasia (CAH) caused by P450 oxidoreductase deficiency (PORD) in 46, XX patients is characterized by genital ambiguity, primary amenorrhea, absent or incomplete sexual maturation, infertility, skeletal malformations and so on. But few pregnancies have been reported from these female patients with PORD.Case descriptionA 29-year-old Chinese woman with PORD due to the compound heterozygous mutation (c.1370G > A/c.1196_1204del) in the P450 oxidoreductase (POR) gene had suffered from primary amenorrhea and infertility. She had one cancelled cycle of ovulation induction due to low serum estradiol(E2), high progesterone(P) levels and thin endometrium, then in vitro fertilization (IVF) was recommended. At the first IVF cycle, 4 oocytes were retrieved and 4 viable embryos were cryopreserved due to thin endometrium associated with low E2 and prematurely elevated P after ovarian stimulation, even though oral dexamethasone were used to control adrenal P overproduction at the same time. When basal P fell to < 1.5 ng/ml after the therapy of oral dexamethasone, artificial endometrial preparation and frozen embryo transfer were performed, resulting in a twin pregnancy. She delivered a healthy boy and a healthy girl by caesarean section at 37 weeks and 2 days of gestation. After the literature search in PORD women, no spontaneous pregnancy has been reported and only two previous case reports of 3 successful pregnancies through IVF were summarized.ConclusionsIt is the third report that successful pregnancy was achieved in a CAH woman caused by a compound heterozygous POR mutation, with primary amenorrhea and disorders of steroidogenesis. It seemed that disorders of steroidogenesis caused by PORD didn’t impair the developmental potential of oocytes. IVF and frozen embryo transfer after adequate hormonal control and endometrial preparation should be an effective infertility treatment for PORD women.

Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage.

Mesolimbic dopamine transmission is dysregulated in multiple psychiatric disorders, including addiction. Previous studies found that the endogenous GABAergic steroid (3α,5α)-3-hydroxy-5-pregnan-20-one (allopregnanolone) modulates dopamine levels in the nucleus accumbens and prefrontal cortex. As allopregnanolone is a potent positive allosteric modulator of GABAA receptors, and GABAA receptors can regulate dopamine release, we hypothesized that allopregnanolone would reduce phasic fluctuations in mesolimbic dopamine release that are important in learning and reward processing. We used fast-scan cyclic voltammetry in anesthetized female and male rats to measure dopamine release in the nucleus accumbens evoked by electrical stimulation of the ventral tegmental area, before and after administration of allopregnanolone. Allopregnanolone (7.5–25 mg/kg, IP) reduced evoked dopamine release in both male and female rats, compared to β-cyclodextrin vehicle. In males, all doses of allopregnanolone decreased dopamine transmission, with stronger effects at 15 and 25 mg/kg allopregnanolone. In females, 15 and 25 mg/kg allopregnanolone reduced dopamine release, while 7.5 mg/kg allopregnanolone was no different from vehicle. Since allopregnanolone is derived from progesterone, we hypothesized that high endogenous progesterone levels would result in lower sensitivity to allopregnanolone. Consistent with this, females in proestrus (high progesterone levels) were less responsive to allopregnanolone than females in other estrous cycle stages. Furthermore, 30 mg/kg progesterone reduced evoked dopamine release in males, similar to allopregnanolone. Our findings confirm that allopregnanolone reduces evoked dopamine release in both male and female rats. Moreover, sex and the estrous cycle modulated this effect of allopregnanolone. These results extend our knowledge about the pharmacological effects of neurosteroids on dopamine transmission, which may contribute to their therapeutic effects.

39 Concentration of obestatin in different stages of ovarian activity in cattle

The objective of the present study was to measure serum levels of obestatin by ELISA with the purpose of establishing parameters and being able to use it as an endocrine marker for the selection of reproductive characteristics of milk and beef cattle. In test 1, 15 Creole cows with genetic tendencies of Charolais, Angus, Brangus, and Gelbvieh were sampled in diestrus and 15 in proestrus, determining their structures with an Aloka Prosound ultrasound with a 7.5-MHz linear transducer. In test 2, 16 Holstein cows were sampled in 2 different ovarian stages, diestrus and proestrus. The standardized technique was a bovine obestatin 96-well ELISA kit from My Biosource Inc. The data were analysed by measuring central tendency and linear regression, where the average levels of obestatin were related to the corpus luteum size and size and number of follicles in milk and beef cattle. We found average levels of 556.99 and 453.35 pg for beef and dairy cattle, respectively (P&amp;lt;0.05). We also found a significant difference (P&amp;lt;0.05) in obestatin concentrations depending on the size of the follicles (751.74, 615.33, and 357.39 pg for follicles of 15, 10, and 5mm, respectively). We found a significant difference in concentration of obestatin (644.53, 550.69, and 455.88 pg; P&amp;lt;0.05) for corpus luteum sizes of &amp;gt;20mm, 10–20mm, and &amp;lt;10mm, respectively. In dairy cattle, obestatin levels were also evaluated at different stages of the cycle, and we found concentrations of 414.79 pg in diestrus and 530.48 pg in proestrus (P&amp;lt;0.05). We conclude that obestatin concentration is positively associated with a greater number and size of follicles as well as with larger corpus luteum because its effect on cell proliferation interacting positively with high levels of progesterone in the blood. We found higher concentrations in beef cattle than in dairy cattle.

122 Colour-Doppler ultrasonography as a tool for oocyte donor selection

Colour-Doppler ultrasonography (CDU) has been applied for a more detailed examination of the ovary and uterus, mainly local blood flow in ovarian follicles and the corpus luteum (CL). The main use of CDU is for the diagnosis of early pregnancy or the selection of recipients for embryo transfer in cattle; however, this tool can also be used to select oocyte donors according to blood flow to the ovary. The concept is that more blood flow in the ovary is conducive to a healthier intraovarian environment (e.g. higher progesterone levels and removal of reactive oxygen species), yielding higher quality oocytes. The objective of this research was to evaluate invitro embryo production (IVP) after selection of oocyte donors, considering ovary irrigation before ovum pickup (OPU). The research was carried out in the reproduction laboratory at the Palominos Ranch (Jalisco, México). The oocyte donors (n=15) were synchronized before each round of OPU using an intravaginal device (1.9g of progesterone) with oestradiol benzoate (2mg) and cloprostenol sodium (500µg) on Day 0, to avoid the presence of a corpus luteum and to synchronize the follicular wave. On Day 6, the intravaginal device was removed and OPU was performed. All Angus breed donors between 3 and 5 years old with a body condition score between 5–6 (scale 1–9, where 1 is extremely thin and 9 is very obese) and were evaluated with transrectal CDU (Sonoscape S2™) with a linear-array probe (7.5MHz) before the first OPU session only. The oocyte donors were classified subjectively into three categories: low blood flow (LBF, ∼30% ovarian area), median blood flow (MBF, ∼50% ovarian area), and high blood flow (HBF, ∼70% ovarian area) and were submitted to 3 cycles of IVP each (45 total cycles). Semen from a proven bull for IVF was used during all IVP cycles. All oocytes collected from each donor were used in IVF with the same semen in all IVP cycles. The total oocytes collected, and percentages of viable oocytes, cleavage, and blastocysts on Day 7 of culture were evaluated. Statistical analysis was carried out using the GLM procedure of SAS software (version 9.3; SAS Institute Inc.) to evaluate the results of LBF, MBF, and HBF (P-value=0.05). Total oocyte recovery was 11.28±1.92, 10.06±1.31, and 15.52±1.05 for HBF, MBF, and LBF, respectively, being significantly higher for LBF (P&amp;lt;0.05). There were no differences in viable oocytes among groups. Cleavage rates were 53.04%±3.43 for HBF, 43.18%±2.34 for MBF, and 43.69%±1.89 for LBF, being significantly higher for HBF (P&amp;lt;0.05). Percentage of blastocysts on Day 7 was 38.16%±3.80 for HBF, 30.11%±2.60 for MBF, and 17.78%±2.10 for LBF. This value tended to be significantly higher for HBF than MBF, and both were significantly superior to LBF (P&amp;lt;0.05). In conclusion, under the conditions of this research, although LBF donors had more total recovered oocytes, blastocyst rates were increased in HBF and MBF donors. Therefore, based on the results of the present study, CDU can be a useful tool for the selection of oocyte donors.

Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation.

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre‐sleep and post‐sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.

Progesterone Intramuscularly or Vaginally Administration May Not Change Live Birth Rate or Neonatal Outcomes in Artificial Frozen-Thawed Embryo Transfer Cycles.

BackgroundsPrevious studies suggested that singletons from frozen-thawed embryo transfer (FET) were associated with higher risk of large, post-date babies and adverse obstetrical outcomes compared to fresh transfer and natural pregnancy. No data available revealed whether the adverse perinatal outcomes were associated with aberrantly high progesterone level from different endometrium preparations in HRT-FET cycle. This study aimed to compare the impact of progesterone intramuscularly and vaginally regimens on neonatal outcomes in HRT-FET cycles.MethodsA total of 856 HRT-FET cycles from a fertility center from 2015 to 2018 were retrospectively analyzed. All patients had their first FET with two cleavage-staged embryos transferred. Endometrial preparation was performed with sequential administration of estrogen followed by progesterone intramuscularly 60 mg per day or vaginal gel Crinone 90 mg per day. Pregnancy outcomes including live birth rate, singleton birthweight, large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm delivery rate were analyzed. Student’s t test, Mann-Whitney U-test, Chi square analysis, and multivariable logistic regression were used where appropriate. Differences were considered significant if p < 0.05.ResultsNo significant difference of live birth rate was found between different progesterone regimens (Adjusted OR 1.128, 95% CI 0.842, 1.511, p = 0.420). Neonatal outcomes like singleton birthweight (p = 0.744), preterm delivery rate (Adjusted OR 1.920, 95% CI 0.603, 6.11, p = 0.269), SGA (Adjusted OR 0.227, 95% CI 0.027, 1.934, p = 0.175), and LGA rate (Adjusted OR 0.862, 95% CI 0.425, 1.749, p=0.681) were not different between two progesterone regimens. Serum P level >41.82 pmol/L at 14 day post-FET was associated with higher live birth rate than serum P level ≤41.82 pmol/L in HRT-FET cycles when progesterone was intramuscularly delivered (Adjusted OR 1.690, 95% CI 1.002, 2.849, p = 0.049). But singleton birthweight, preterm delivery rate, SGA and LGA rate were not different between these two groups.ConclusionsRelatively higher serum progesterone level induced by intramuscular regimen did not change live birth rate or neonatal outcomes compared to vaginal regimen. Monitoring serum progesterone level and optimizing progesterone dose of intramuscular progesterone as needed in HRT-FET cycles has a role in improving live birth rate without impact on neonatal outcomes.

PSVII-34 Reproductive qualities of sows using exogenous progesteron

Abstract The aim of this study was to research the endocrine status and reproductive quality of sows using a prolonged drug containing 15% progesterone. Endocrine status in sows was examined at 9, 11, 16 and 21 days after insemination. The level of progesterone was determined by enzyme immunoassay. The sows of the experimental group (G1, n = 20) were injected in a dose of 2.0 ml on the 10th day after insemination, the sows of the control group (CG, n = 20) were control. It was found that the level of progesterone in the blood of G1 slightly increases from 9 to 11 days after insemination. In the G1, the steroid concentration increased from 2.28 ± 0.23 to 2.35 ± 0.15 nmmol / L, and in the GC from 2.35 ± 0.07 to 2.58 ± 0.10 nmmol / L. On the 16th day after insemination in G1, the progesterone level was accompanied by a sharp rise of 2.7 times (P &amp;lt; 0.001) - to 6.44 ± 0.58 nmmol / L, the level of the hormone in the GC did not change. The high level of progesterone in this critical period favorably affects the implantation of the embryos and causes a further normal course of pregnancy. On the 21st day after insemination, the progesterone concentration in both groups decreased. However, the level of this steroid hormone in the group when using this hormonal agent remained 1.95 times higher (P &amp;lt; 0.05) than in the control. Also, in G1 there is an increase in multiple pregnancy by 11.55%, the number of live newborn piglets by 23.36%, a decrease in the number of stillborn piglets by 2.14 times (P &amp;lt; 0.05) and mummified fetuses by 11.11%, compared with similar indicators of the control group.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

Progesterone induces pyroptosis of p53-defective fimbrial epithelial cells through the paracrine by stromal fibroblast

Objective: Incessant ovulation and fimbrial origin with p53 deficiency have been considered the essential issues for ovarian cancer initiation. We previously reported that a physiologically high level of progesterone (P4) in the ovulating follicular fluid could eliminate p53-defective fimbrial epithelial cells by inducing necroptosis through the TNF-α/RIPK1/RIPK3/MLKL pathway, suggesting a preventive effect against cancer development. Epidemiological studies show that oral pill use can effectively prevent the occurrence of ovarian cancer.

High progesterone levels facilitate women’s social information processing by optimizing attention allocation

Ovarian hormones exert an influence on social information processing, in which, however, the exact roles of estradiol and progesterone remain unclear. This study examines the specific influences of these two ovarian hormones on social information processing across the menstrual cycle using the emotional face flanker task and attentional network test (ANT). Twenty-six naturally cycling, healthy women were tested thrice: during menses, in the follicular phase, and in the luteal phase. In the emotional face flanker task, a significant positive relation was found between progesterone levels and reaction times (RTs) for sad faces, suggesting that high progesterone levels may activate the social monitoring system and allocate more attention to the social stimulus, which benefits individuals’ survival and adaptation. In the ANT, a significant increase was found in RTs and accuracy during the luteal phase, suggesting that luteal women increase this accuracy by exerting a relatively conservative strategy of allocating more attention to the targets. Taken together, these findings indicate that high levels of progesterone may facilitate social information processing by optimizing attention allocation. Moreover, overactivation of the social monitoring system may make women more susceptible to stressors and promote affective disturbances, which may provide underlying pathophysiology of the premenstrual dysphoric disorder.

EMBRYOLOGICAL OUTCOME AND HORMONAL PROFILE AFTER DOUBLE STIMULATION IN PATIENTS WITH POOR PROGNOSIS: INTRA-PATIENT PAIRED STUDY

Stimulation in both phases of the menstrual cycle became a new approach in poor responder patient’s management. Previous studies showed that this approach could be a good opportunity for poor-responder patients because it results in more oocytes and embryos. However, stimulation in the follicular phase makes endocrine and paracrine changes especially in the hormonal profile, which is associated with the corpus luteum function and could lead to changes in the follicle environment during luteal stimulation. Therefore, there is still need for more data about embryological outcomes and hormonal changes after DuoStim, comparing follicular versus luteal phase stimulations in the same ovarian cycle. A total of 76 patients with a reduced ovarian reserve was included in the intra-patient paired study. Inclusion criteria: age <43 years; АМH <1.2 ng/ml; AFC <6; basal FSH≥11 IU/ml. Exclusion criteria: uterine fibroids≥4 cm, deep endometriosis, cancer, BMI ≥29 kg/m2, smoking, severe male infertility. Group 1 (n=76) received stimulation on the day 2 follicular phase (FP). Group 2 (n=76) received the stimulation in the luteal phase (LP) on the 4th day after the first oocyte pick up (OPU) day in the same menstrual cycle. Plasma samples were obtained on stimulation starter day, 6 days after, on triggering and OPU day. Statistical analysis – the Mann-Whitney test, t-test, the chi-squared test; p<0.05 was considered to be statistically significant. The mean age was 36.7± 3.8 years and anti-mullerian hormone concentration was 0.94± 0.3 ng/ml in the patient’s cohort. On the stimulation starting day, the estradiol (E2) and progesterone (P) concentrations were significantly higher in group II LP stimulation patients than in a group I (Table), but then decreased and were similar in both groups on the ovulation triggering day. However, no significant differences in the embryological outcomes were found between the groups (Table). The cohorts of oocytes obtained after the luteal phase are similar to their paired follicular phase derived cohorts, and demonstrate an equal number of the blastocyst and Top-quality blastocysts. High estradiol and progesterone levels on the stimulation starting day did not affect the embryological outcome.Tabled 11 group FP (n=76)2 group LP (n=76)PEstradiol on stimulation start day (pmol/L)87,8±18,1384,27±334,44p<0.001Estradiol trig. day (pmol/L)3670,97±2896,03697,73±2231,34NSProgesterone on stimulation start day (nmol/L)0,88±0,416,7±13,3p<0.001Progesterone trig. day (nmol/L)3,8±4,95,6±4,6NSRetrieved oocytes (n)3.9±2.65.2±3.0NSMII oocytes (n)3.8±2.24.3±2.6NSBlastocysts (n)1.7±1.22.1±2.2NSTOP-blastocysts (n)1.0±0.61.6±0.6NS Open table in a new tab

Abstract MP14: Endothelial Mineralocorticoid Receptor Deletion Abrogates Leptin-induced Endothelial Dysfunction And Fetal Growth Restriction In Pregnant Mice

Obesity increases preeclampsia (PE) risk. Plasma leptin levels increase with body weight in women with PE, and in addition, placental ischemia, an initiating event of PE, also increases plasma leptin. Our lab has shown that hyperleptinemia induces endothelial dysfunction and hypertension in female mice via endothelial mineralocorticoid receptor (ECMR) activation and that high progesterone levels of pregnancy increases ECMR expression. We hypothesized that leptin infusion induces PE-like endothelial dysfunction in pregnant mice, which is abrogated by ECMR deletion. Pregnant mice were infused with leptin by miniosmotic pump (0.9mg/kg/day, s.c.) on gestation day (GD) 11-18. Leptin decreased pup wt (0.86±0.04g ECMR +/+ vs 0.52±0.11 ECMR +/+ +leptin, *P&lt;0.05). and increased fetal resorption (3±39% ECMR +/+ vs 42±32 ECMR +/+ +leptin, P=0.09). ECMR deletion rescued pup weight (0.91±0.06g ECMR -/- vs 1.0±0.07 ECMR -/- +leptin) and protected fetal resorptions (2±2% ECMR -/- vs 0±0 ECMR -/- +leptin) in leptin-infused pregnant mice. In association, placental efficiency (pup/placenta ratio) decreased with leptin in ECMR +/+ (9.7±0.7 ECMR +/+ vs 7.9±0.6 ECMR +/+ +leptin, *P&lt;0.05), but not ECMR -/- (9.6±0.5 ECMR -/- vs 9.4±1.2 ECMR -/- +leptin) mice. Leptin infusion reduced endothelial function (acetylcholine-mediated relaxation) in aortas of ECMR +/+ , but not ECMR -/- , pregnant mice (2-way ANOVA, repeated measures, *P&lt;0.05). Relaxation responses to acetylcholine with LNAME showed restoration of endothelial function in ECMR -/- +leptin mice was due to preserved NO bioavailability. No changes in endothelial-independent sodium nitroprusside or contractile responses to phenylephrine, serotonin or KCl were observed. ECMR deletion reduced aorta IL-1β mRNA (0.5±0.1-fold change ECMR +/+ +leptin vs 0.2±0.1-fold change ECMR -/- +leptin, P=0.06) levels and also placental growth factor mRNA (1.0±0.3-fold change ECMR +/+ +leptin vs 01.3±0.1 ECMR -/- +leptin, P=0.05) in placental tissues. Collectively, these data indicate that ECMR deletion protects pregnant mice from adverse fetal growth and demise in association with increasing NO vascular bioavailability, reducing vascular inflammation and improving placental function in a leptin-infused model of PE.

Regulation of lipid droplets via the PLCβ2-PKCα-ADRP pathway in granulosa cells exposed to cadmium

In steroidogenic cells, steroids are synthesized de novo from cholesterol stored in lipid droplets (LDs). The size of LDs regulated by adipose differentiation-related protein (ADRP) is closely related to cholesterol ester hydrolysis. Many studies reported that cadmium (Cd) had dual effects on steroidogenesis in granulosa cells (GCs). However, the role of LD and its regulation in abnormal steroidogenesis caused by Cd exposure remain unknown. In current study, female rats were exposed to CdCl2 during gestation and lactation, and influence of such exposure was investigated in ovarian GCs of female offspring. The size of LDs was found much smaller than normal in GCs; ADRP was down-regulated and hormone-sensitive lipase (HSL) phosphorylation was increased, followed by up-regulation of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (CYP11A1); the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (PLCβ2) and protein kinase C alpha type (PKCα) were both decreased accompanying the ADRP down-regulation. This series of events resulted in a high level of progesterone in serum. Similar results were demonstrated in GCs treated with 20 μM CdCl2 for 24 h in vitro. The protein level of ADRP was decreased after gene silencing of PLCβ2/PKCα, and the knockdown of PLCβ2/PKCα/ADRP led to micro-sized LD formation. We found that Cd exposure down-regulated ADRP by inhibiting the PLCβ2-PKCα signaling pathway, reduced the size of LDs, and promoted HSL phosphorylation. StAR and CYP11A1 were both up-regulated following the hydrolysis of cholesterol ester, which led to a high production of progesterone. LD thereby is a target subcellular organelle for Cd to affect steroid hormone synthesis in ovarian GCs. These findings might help to uncover the mechanism of ovarian dysfunction and precocious puberty caused by Cd pollution.